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  • International Union of Crystallography (IUCr)
  • Annual Reviews
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  • 1
    Journal cover
    Unbekannt
    Wiley-Blackwell - STM | International Union of Crystallography (IUCr)
    Online: 1(1).1994 –
    Verlag: Wiley-Blackwell - STM , International Union of Crystallography (IUCr)
    Print ISSN: 0909-0495
    Digitale ISSN: 1600-5775
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Journal cover
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    International Union of Crystallography (IUCr) | Wiley
    Online: 53.1997 –
    Online: 53.1997 –
    Vormals: Acta Crystallographica  (1948–1967)
    Verlag: International Union of Crystallography (IUCr) , Wiley
    Körperschaft: International Union of Crystallography, IUCr
    Print ISSN: 0108-7673 , 0567-7394
    Digitale ISSN: 1600-5724 , 1600-8596 , 2053-2733
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Journal cover
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    International Union of Crystallography (IUCr) | Wiley
    Online: 61.2005 –
    Online: 61.2005 –
    Verlag: International Union of Crystallography (IUCr) , Wiley
    Print ISSN: 1744-3091
    Digitale ISSN: 2053-230X
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
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    Annual Reviews
    Online: 1973 – 1996
    Verlag: Annual Reviews
    Print ISSN: 0084-6597
    Digitale ISSN: 1545-4495
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
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    Annual Reviews
    Online: 1.2013 – 4.2016
    Online: 1.2013 – 4.2016
    Verlag: Annual Reviews
    Print ISSN: 2165-8102
    Digitale ISSN: 2165-8110
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
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    Annual Reviews
    Online: 1.2008 – 9.2016
    Online: 1.2008 – 9.2016
    Verlag: Annual Reviews
    Print ISSN: 1936-1327
    Digitale ISSN: 1936-1335
    Thema: Chemie und Pharmazie
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
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    Annual Reviews
    Online: 1.1972 – 45.2016
    Online: 1.1972 – 45.2016
    Verlag: Annual Reviews
    Print ISSN: 0084-6570
    Digitale ISSN: 1545-4290
    Thema: Biologie , Ethnologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
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    Annual Reviews
    Online: 1.2009 – 8.2016
    Online: 1.2009 – 8.2016
    Verlag: Annual Reviews
    Print ISSN: 1941-1405
    Digitale ISSN: 1941-0611
    Thema: Biologie , Geologie und Paläontologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
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    Annual Reviews
    Online: 1.1978 – 39.2016
    Online: 1.1978 – 39.2016
    Verlag: Annual Reviews
    Print ISSN: 0147-006X
    Digitale ISSN: 1545-4126
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Journal cover
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    Annual Reviews
    Online: 1.2009 – 5.2013
    Verlag: Annual Reviews
    Print ISSN: 1941-1340
    Digitale ISSN: 1941-1359
    Thema: Wirtschaftswissenschaften
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
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    International Union of Crystallography (IUCr)
    Online: 1.1948 – 23.1967
    Verlag: International Union of Crystallography (IUCr)
    Print ISSN: 0365-110X
    Digitale ISSN: 1600-8642
    Thema: Geologie und Paläontologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Journal cover
    Unbekannt
    International Union of Crystallography (IUCr) | Wiley
    Online: 53.1997 –
    Online: 53.1997 –
    Vormals: Acta Crystallographica  (1948–1967)
    Verlag: International Union of Crystallography (IUCr) , Wiley
    Körperschaft: International Union of Crystallography, IUCr
    Print ISSN: 0108-7681 , 0567-7408 , 2052-5192
    Digitale ISSN: 1600-5740 , 1600-8650 , 2052-5206
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
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    International Union of Crystallography (IUCr)
    Online: 57.2001 – 63.2007
    Verlag: International Union of Crystallography (IUCr)
    Körperschaft: International Union of Crystallography, IUCr
    Digitale ISSN: 1600-5368
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
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    International Union of Crystallography (IUCr) | Wiley
    Online: 53.1997 – 66.2010
    Online: 53.1997 –
    Vormals: Crystal Structure Communications  (1972–1982)
    Verlag: International Union of Crystallography (IUCr) , Wiley
    Körperschaft: International Union of Crystallography, IUCr
    Print ISSN: 0108-2701 , 2053-2296
    Digitale ISSN: 1600-5759 , 2053-2296
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
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    Annual Reviews | JSTOR
    Online: 1.2009 – 5.2013
    Verlag: Annual Reviews , JSTOR
    Print ISSN: 1941-1367
    Digitale ISSN: 1941-1375
    Thema: Wirtschaftswissenschaften
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
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    Annual Reviews
    Online: 1.1983 – 34.2016
    Online: 1.1983 – 34.2016
    Verlag: Annual Reviews
    Print ISSN: 0732-0582
    Digitale ISSN: 1545-3278
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
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    Annual Reviews
    Online: 1.1971 – 46.2016
    Online: 1.1971 – 46.2016
    Vormals: Annual Review of Materials Science  (1971–2000)
    Verlag: Annual Reviews
    Print ISSN: 0084-6600 , 1531-7331
    Digitale ISSN: 1545-4118
    Thema: Maschinenbau
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
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    Annual Reviews
    Online: 1.2017 –
    Verlag: Annual Reviews
    Digitale ISSN: 2472-3428
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
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    Annual Reviews
    Online: 1.1999 – 18.2016
    Online: 1.1999 – 18.2016
    Online: 1.2021 –
    Verlag: Annual Reviews
    Print ISSN: 1523-9829
    Digitale ISSN: 1545-4274
    Thema: Medizin , Technik allgemein
    Standort Signatur Erwartet Verfügbarkeit
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  • 20
    Vormals: Annual Review of Biophysics and Biomolecular Structure ; Annual Review of Biophysics and Biophysical Chemistry ; Annual Review of Biophysics and Bioengineering  (1972–2007)
    Verlag: Annual Reviews
    Print ISSN: 0084-6589 , 0883-9182 , 1056-8700 , 1936-122X
    Digitale ISSN: 1545-4266 , 1936-1238
    Thema: Biologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 21
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    Annual Reviews
    Online: 1.1986 – 4.1990
    Online: 1.1986 – 4.1990
    Verlag: Annual Reviews
    Print ISSN: 8756-7016
    Digitale ISSN: 8756-7016
    Thema: Informatik
    Standort Signatur Erwartet Verfügbarkeit
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  • 22
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    Annual Reviews
    Online: 1.2000 –
    Online: 1.2021 –
    Verlag: Annual Reviews
    Print ISSN: 1527-8204
    Digitale ISSN: 1545-293X
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 23
    Journal cover
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    Annual Reviews | JSTOR
    Online: 1.2009 – 5.2013
    Verlag: Annual Reviews , JSTOR
    Print ISSN: 1941-1383
    Digitale ISSN: 1941-1391
    Thema: Wirtschaftswissenschaften
    Standort Signatur Erwartet Verfügbarkeit
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  • 24
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    Annual Reviews
    Online: 1.1956 – 61.2016
    Online: 1.1956 – 61.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4170
    Digitale ISSN: 1545-4487
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 25
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    Annual Reviews
    Online: 1.1967 – 50.2016
    Online: 1.1967 – 50.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4197
    Digitale ISSN: 1545-2948
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 26
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    Annual Reviews
    Online: 1.1947 – 70.2016
    Online: 1.1947 – 70.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4227
    Digitale ISSN: 1545-3251
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 27
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    Annual Reviews
    Online: 1.1981 – 36.2016
    Online: 1.1981 – 36.2016
    Verlag: Annual Reviews
    Print ISSN: 0199-9885
    Digitale ISSN: 1545-4312
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Standort Signatur Erwartet Verfügbarkeit
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  • 28
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    Annual Reviews
    Online: 1.1985 – 32.2016
    Online: 1.1985 – 32.2016
    Vormals: Annual Review of Cell Biology  (1985–1994)
    Verlag: Annual Reviews
    Print ISSN: 0743-4634 , 1081-0706
    Digitale ISSN: 1530-8995
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 29
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    Annual Reviews
    Online: 1.2010 – 7.2016
    Online: 1.2010 – 7.2016
    Verlag: Annual Reviews
    Print ISSN: 1947-5454
    Digitale ISSN: 1947-5462
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 30
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    Annual Reviews
    Online: 1.1963 – 54.2016
    Online: 1.1963 – 54.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4146
    Digitale ISSN: 1545-4282
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 31
    Journal cover
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    Annual Reviews
    Online: 1.1973 –
    Print: 8.1980 – 46.2018 (Ort: A17, Kompaktmagazin, 5/6-7)
    Verlag: Annual Reviews
    Print ISSN: 0084-6597
    Digitale ISSN: 1545-4495
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 32
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    Annual Reviews
    Online: 1.1976 –
    Online: 1.1976 –
    Vormals: Annual Review of Energy and the Environment ; Annual Review of Energy  (1976–2002)
    Verlag: Annual Reviews
    Print ISSN: 0362-1626 , 1056-3466 , 1543-5938
    Digitale ISSN: 1545-2050
    Thema: Energietechnik
    Standort Signatur Erwartet Verfügbarkeit
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  • 33
    Journal cover
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    International Union of Crystallography (IUCr) | Wiley
    Online: 53.1997 –
    Online: 53.1997 –
    Verlag: International Union of Crystallography (IUCr) , Wiley
    Körperschaft: International Union of Crystallography, IUCr
    Print ISSN: 0907-4449
    Digitale ISSN: 1399-0047 , 2059-7983
    Thema: Chemie und Pharmazie , Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 34
    Journal cover
    Unbekannt
    International Union of Crystallography (IUCr)
    Online: 64.2008 –
    Verlag: International Union of Crystallography (IUCr)
    Körperschaft: International Union of Crystallography, IUCr
    Digitale ISSN: 1600-5368 , 2056-9890
    Thema: Chemie und Pharmazie , Geologie und Paläontologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 35
    Journal cover
    Unbekannt
    International Union of Crystallography (IUCr)
    Online: 61.2005 –
    Verlag: International Union of Crystallography (IUCr)
    Print ISSN: 2053-230X
    Digitale ISSN: 1744-3091
    Thema: Chemie und Pharmazie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 36
    Journal cover
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    Annual Reviews
    Online: 1.1952 –
    Online: 1.1952 –
    Vormals: Annual Review of Nuclear Science  (1952–1977)
    Verlag: Annual Reviews
    Print ISSN: 0066-4243 , 0163-8998
    Digitale ISSN: 1545-4134
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 37
    Journal cover
    Unbekannt
    Annual Reviews
    Online: 1.1961 – 56.2016
    Online: 1.1961 – 56.2016
    Vormals: Annual Review of Pharmacology  (1961–1975)
    Verlag: Annual Reviews
    Print ISSN: 0066-4251 , 0362-1642
    Digitale ISSN: 1545-4304
    Thema: Chemie und Pharmazie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 38
    Journal cover
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    Annual Reviews
    Online: 1.1963 – 54.2016
    Online: 1.1963 – 54.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4286
    Digitale ISSN: 1545-2107
    Thema: Biologie , Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft
    Standort Signatur Erwartet Verfügbarkeit
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  • 39
    Journal cover
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    Annual Reviews
    Online: 1.2014 – 3.2016
    Online: 1.2014 – 3.2016
    Verlag: Annual Reviews
    Print ISSN: 2326-8298
    Digitale ISSN: 2326-831X
    Thema: Mathematik
    Standort Signatur Erwartet Verfügbarkeit
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  • 40
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    Annual Reviews
    Online: 1963 – 1995
    Verlag: Annual Reviews
    Print ISSN: 0066-4146
    Digitale ISSN: 1545-4282
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 41
    Journal cover
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    Annual Reviews
    Online: 1.1932 – 85.2016
    Online: 1.1932 – 85.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4154
    Digitale ISSN: 1545-4509
    Thema: Biologie , Chemie und Pharmazie
    Standort Signatur Erwartet Verfügbarkeit
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  • 42
    Journal cover
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    Annual Reviews
    Online: 1.1970 – 47.2016
    Online: 1.1970 – 47.2016
    Vormals: Annual Review of Ecology and Systematics  (1970–2002)
    Verlag: Annual Reviews
    Print ISSN: 0066-4162 , 1543-592X
    Digitale ISSN: 1545-2069
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 43
    Journal cover
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    Annual Reviews
    Online: 1.1969 – 48.2016
    Online: 1.1969 – 48.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4189
    Digitale ISSN: 1545-4479
    Thema: Maschinenbau , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 44
    Journal cover
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    Annual Reviews
    Online: 1.1939 – 78.2016
    Online: 1.1939 – 78.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-4278
    Digitale ISSN: 1545-1585
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 45
    Journal cover
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    Annual Reviews
    Online: 1.1950 – 67.2016
    Online: 1.1950 – 67.2016
    Vormals: Annual Review of Plant Physiology and Plant Molecular Biology ; Annual Review of Plant Physiology  (1950–2001)
    Verlag: Annual Reviews
    Print ISSN: 0066-4294 , 1040-2519 , 1543-5008
    Digitale ISSN: 1545-2123
    Thema: Biologie
    Standort Signatur Erwartet Verfügbarkeit
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  • 46
    Journal cover
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    Annual Reviews
    Online: 1.1950 – 67.2016
    Online: 1.1950 – 67.2016
    Verlag: Annual Reviews
    Print ISSN: 0066-426X
    Digitale ISSN: 1545-1593
    Thema: Chemie und Pharmazie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 47
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    Wiley-Blackwell - STM | International Union of Crystallography (IUCr)
    Online: 1(1).1968 –
    Print: 26.1993 – 30.1997 (Ort: A17, Archiv, Magazin, 30/5)
    Verlag: Wiley-Blackwell - STM , International Union of Crystallography (IUCr)
    Print ISSN: 0021-8898
    Digitale ISSN: 1600-5767
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 48
    Journal cover
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    Annual Reviews
    Online: 2017 –
    Verlag: Annual Reviews
    Beschreibung: What is known? What isn’t known? Knowable Magazine, the digital publication from Annual Reviews, seeks to make that knowledge accessible to all. Knowable Magazine explores the real-world significance of scholarly work through a journalistic lens. We report on the current state of play across a wide variety of fields — from agriculture to high-energy physics; biochemistry to water security; the origins of the universe to psychology. Review articles written by leading scholars from the 50 Annual Reviews journals serve as springboards for stories in Knowable Magazine. Through in-depth features, explainers, articles, essays, interviews, infographics, slideshows, and comics, Knowable Magazine presents insights from research to a broader audience. The content is published under a CC BY-ND copyright license, and the Annual Reviews journal articles featured in Knowable Magazine are free to all for a limited period. Knowable Magazine content is thoroughly researched, reported, edited, copy-edited and fact-checked. Review articles in Annual Review journals provide ideas, but editorial decisions and reporting decisions are made by the magazine staff, guided by what will best inform and intrigue readers.
    Digitale ISSN: 2575-4459
    Thema: Allgemeine Naturwissenschaft
    Schlagwort(e): Allgemeine Naturwissenschaften ; Forschung
    Standort Signatur Erwartet Verfügbarkeit
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  • 49
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    International Union of Crystallography (IUCr)
    Online: 6(1).1998 –
    Verlag: International Union of Crystallography (IUCr)
    Print ISSN: 1067-0696
    Digitale ISSN: 1945-0834
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 50
    Journal cover
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    International Union of Crystallography (IUCr)
    Online: 1(1).2014 –
    Verlag: International Union of Crystallography (IUCr)
    Digitale ISSN: 2052-2525
    Thema: Geologie und Paläontologie , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 51
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    Annual Reviews
    In:  EPIC3Annu. Rev. Mar. Sci., Annual Reviews, 4, pp. 143-176
    Publikationsdatum: 2019-07-17
    Beschreibung: The public health, tourism, fisheries, and ecosystem impacts from harmful algal blooms (HABs) have all increased over the past few decades. This has led to heightened scientific and regulatory attention, and the development of many new technologies and approaches for research and management. This, in turn, is leading to significant paradigm shifts with regard to, e.g.,our interpretation of the phytoplankton species concept (strain variation), the dogma of their apparent cosmopolitanism, the role of bacteria and zooplankton grazing in HABs, and our approaches to investigating the ecological and genetic basis for the production of toxins and allelochemicals. Increasingly,eutrophication and climate change are viewed andmanaged as multifactorial environmental stressors that will further challenge managers of coastal resources and those responsible for protecting human health. Here we review HABscience with an eye toward new concepts and approaches,emphasizing, where possible, the unexpected yet promising new directions that research has taken in this diverse field.
    Repository-Name: EPIC Alfred Wegener Institut
    Materialart: Article , isiRev
    Format: application/pdf
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  • 52
    Publikationsdatum: 2022-05-25
    Beschreibung: Author Posting. © Annual Reviews, 2003. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Environment and Resources 28 (2003): 521-558, doi:10.1146/annurev.energy.28.011503.163443.
    Beschreibung: Agriculture and industrial development have led to inadvertent changes in the natural carbon cycle. As a consequence, concentrations of carbon dioxide and other greenhouse gases have increased in the atmosphere and may lead to changes in climate. The current challenge facing society is to develop options for future management of the carbon cycle. A variety of approaches has been suggested: direct reduction of emissions, deliberate manipulation of the natural carbon cycle to enhance sequestration, and capture and isolation of carbon from fossil fuel use. Policy development to date has laid out some of the general principles to which carbon management should adhere. These are summarized as: how much carbon is stored, by what means, and for how long. To successfully manage carbon for climate purposes requires increased understanding of carbon cycle dynamics and improvement in the scientific capabilities available for measurement as well as for policy needs. The specific needs for scientific information to underpin carbon cycle management decisions are not yet broadly known. A stronger dialogue between decision makers and scientists must be developed to foster improved application of scientific knowledge to decisions. This review focuses on the current knowledge of the carbon cycle, carbon measurement capabilities (with an emphasis on the continental scale) and the relevance of carbon cycle science to carbon sequestration goals.
    Beschreibung: The National Center for Atmospheric Research is supported by the National Science Foundation.
    Schlagwort(e): Carbon sequestration ; Measurement techniques ; Climate ; Kyoto protocol
    Repository-Name: Woods Hole Open Access Server
    Materialart: Article
    Format: 406392 bytes
    Format: application/pdf
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  • 53
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    Annual Reviews
    Publikationsdatum: 2022-05-25
    Beschreibung: Author Posting. © Annual Reviews, 2006. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Fluid Mechanics 38 (2006): 395-425, doi:10.1146/annurev.fluid.38.050304.092129.
    Beschreibung: Over the past four decades, the combination of in situ and remote sensing observations has demonstrated that long nonlinear internal solitary-like waves are ubiquitous features of coastal oceans. The following provides an overview of the properties of steady internal solitary waves and the transient processes of wave generation and evolution, primarily from the point of view of weakly nonlinear theory, of which the Korteweg-de Vries equation is the most frequently used example. However, the oceanographically important processes of wave instability and breaking, generally inaccessible with these models, are also discussed. Furthermore, observations often show strongly nonlinear waves whose properties can only be explained with fully nonlinear models.
    Beschreibung: KRH acknowledges support from NSF and ONR and an Independent Study Award from the Woods Hole Oceanographic Institution. WKM acknowledges support from NSF and ONR, which has made his work in this area possible, in close collaboration with former graduate students at Scripps Institution of Oceanography and MIT.
    Schlagwort(e): Solitary waves ; Nonlinear waves ; Stratified flow ; Physical Oceanography
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  • 54
    Publikationsdatum: 2022-05-25
    Beschreibung: First published online as a Review in Advance on October 24, 2005. (Some corrections may occur before final publication online and in print)
    Beschreibung: Author Posting. © Annual Reviews, 2005. This article is posted here by permission of Annual Reviews for personal use, not for redistribution. The definitive version was published in Annual Review of Physiology 68 (2006): 22.1-22.29, doi:10.1146/annurev.physiol.68.040104.105418.
    Beschreibung: Superfast muscles of vertebrates power sound production. The fastest, the swimbladder muscle of toadfish, generates mechanical power at frequencies in excess of 200 Hz. To operate at these frequencies, the speed of relaxation has had to increase approximately 50-fold. This increase is accomplished by modifications of three kinetic traits: (a) a fast calcium transient due to extremely high concentration of sarcoplasmic reticulum (SR)-Ca2+ pumps and parvalbumin, (b) fast off-rate of Ca2+ from troponin C due to an alteration in troponin, and (c) fast cross-bridge detachment rate constant (g, 50 times faster than that in rabbit fast-twitch muscle) due to an alteration in myosin. Although these three modifications permit swimbladder muscle to generate mechanical work at high frequencies (where locomotor muscles cannot), it comes with a cost: The high g causes a large reduction in attached force-generating cross-bridges, making the swimbladder incapable of powering low-frequency locomotory movements. Hence the locomotory and sound-producing muscles have mutually exclusive designs.
    Beschreibung: This work was made possible by support from NIH grants AR38404 and AR46125 as well as the University of Pennsylvania Research Foundation.
    Schlagwort(e): Parvalbumin ; Ca2+ release ; Ca2+ uptake ; Cross-bridges ; Adaptation ; Sound production ; Whitman Center
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  • 55
    Publikationsdatum: 2022-10-27
    Beschreibung: This paper is not subject to U.S. copyright. The definitive version was published in Sherwood, C. R., van Dongeren, A., Doyle, J., Hegermiller, C. A., Hsu, T.-J., Kalra, T. S., Olabarrieta, M., Penko, A. M., Rafati, Y., Roelvink, D., van der Lugt, M., Veeramony, J., & Warner, J. C. Modeling the morphodynamics of coastal responses to extreme events: what shape are we in? Annual Review of Marine Science, 14, (2022): 457–492, https://doi.org/10.1146/annurev-marine-032221-090215.
    Beschreibung: This review focuses on recent advances in process-based numerical models of the impact of extreme storms on sandy coasts. Driven by larger-scale models of meteorology and hydrodynamics, these models simulate morphodynamics across the Sallenger storm-impact scale, including swash,collision, overwash, and inundation. Models are becoming both wider (as more processes are added) and deeper (as detailed physics replaces earlier parameterizations). Algorithms for wave-induced flows and sediment transport under shoaling waves are among the recent developments. Community and open-source models have become the norm. Observations of initial conditions (topography, land cover, and sediment characteristics) have become more detailed, and improvements in tropical cyclone and wave models provide forcing (winds, waves, surge, and upland flow) that is better resolved and more accurate, yielding commensurate improvements in model skill. We foresee that future storm-impact models will increasingly resolve individual waves, apply data assimilation, and be used in ensemble modeling modes to predict uncertainties.
    Beschreibung: All authors except D.R. were partially supported by the IFMSIP project, funded by US Office of Naval Research grant PE 0601153N under contracts N00014-17-1-2459 (Deltares), N00014-18-1-2785 (University of Delaware), N0001419WX00733 (US Naval Research Laboratory, Monterey), N0001418WX01447 (US Naval Research Laboratory, Stennis Space Center), and N0001418IP00016 (US Geological Survey). C.R.S., C.A.H., T.S.K., and J.C.W. were supported by the US Geological Survey Coastal/Marine Hazards and Resources Program. A.v.D. and M.v.d.L. were supported by the Deltares Strategic Research project Quantifying Flood Hazards and Impacts. M.O. acknowledges support from National Science Foundation project OCE-1554892.
    Schlagwort(e): Coastal morphodynamics ; Extreme storms ; Coastal modeling ; Sandy coasts ; Waves ; Sediment transport
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  • 56
    Publikationsdatum: 2022-05-26
    Beschreibung: © The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Annual Review of Marine Science 9 (2017): 173-203, doi:10.1146/annurev-marine-010816-060733.
    Beschreibung: The events that followed the Tohoku earthquake and tsunami on March 11, 2011, included the loss of power and overheating at the Fukushima Daiichi nuclear power plants, which led to extensive releases of radioactive gases, volatiles, and liquids, particularly to the coastal ocean. The fate of these radionuclides depends in large part on their oceanic geochemistry, physical processes, and biological uptake. Whereas radioactivity on land can be resampled and its distribution mapped, releases to the marine environment are harder to characterize owing to variability in ocean currents and the general challenges of sampling at sea. Five years later, it is appropriate to review what happened in terms of the sources, transport, and fate of these radionuclides in the ocean. In addition to the oceanic behavior of these contaminants, this review considers the potential health effects and societal impacts.
    Beschreibung: K.B. was supported in part by the Gordon and Betty Moore Foundation and the Deerbrook Charitable Trust. P.M. was supported in part by the Generalitat de Catalunya through MERS (grant 2014 SGR 1356), the European Commission 7th Framework COMET-FRAME project (grant agreement 604974), and the Ministerio de Economía y Competitividad of Spain (project CTM2011-15152-E). S.C. was supported in part by the French program Investissement d'Avenir run by the National Research Agency (AMORAD project, grant ANR-11-RSNR-0002). D.O. was supported in part by the Center for Environmental Radioactivity (NFR Centers of Excellence grant 223268/F50). J.N.S. was supported in part by the Marine Environmental Observation, Prediction, and Response Network.
    Schlagwort(e): Cesium ; Caesium ; North Pacific ; Radioactivity ; Japan
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  • 57
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    Annual Reviews
    Publikationsdatum: 2023-02-28
    Beschreibung: © The Author(s), 2023. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Timmermans, M.-L., & Toole, J. The Arctic Ocean’s Beaufort Gyre. Annual Review of Marine Science, 15(1), (2023): 223-248, https://doi.org/10.1146/annurev-marine-032122-012034.
    Beschreibung: The Arctic Ocean's Beaufort Gyre is a dominant feature of the Arctic system, a prominent indicator of climate change, and possibly a control factor for high-latitude climate. The state of knowledge of the wind-driven Beaufort Gyre is reviewed here, including its forcing, relationship to sea-ice cover, source waters, circulation, and energetics. Recent decades have seen pronounced change in all elements of the Beaufort Gyre system. Sea-ice losses have accompanied an intensification of the gyre circulation and increasing heat and freshwater content. Present understanding of these changes is evaluated, and time series of heat and freshwater content are updated to include the most recent observations.
    Beschreibung: Support was provided by the National Science Foundation Office of Polar Programs and the Office of Naval Research.
    Schlagwort(e): Arctic Ocean ; Beaufort Gyre ; Circulation ; Sea ice ; Freshwater ; Ocean heat content
    Repository-Name: Woods Hole Open Access Server
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  • 58
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 16(1), pp. 417-441, ISSN: 1941-1405
    Publikationsdatum: 2024-03-01
    Beschreibung: The genus Phaeocystis is globally distributed, with blooms commonly occurring on continental shelves. This unusual phytoplankter has two major morphologies: solitary cells and cells embedded in a gelatinous matrix. Only colonies form blooms. Their large size (commonly 2 mm but up to 3 cm) and mucilaginous envelope allow the colonies to escape predation, but data are inconsistent as to whether colonies are grazed. Cultured Phaeocystis can also inhibit the growth of co-occurring phytoplankton or the feeding of potential grazers. Colonies and solitary cells use nitrate as a nitrogen source, although solitary cells can also grow on ammonium. Phaeocystis colonies might be a major contributor to carbon flux to depth, but in most cases, colonies are rapidly remineralized in the upper 300 m. The occurrence of large Phaeocystis blooms is often associated with environments with low and highly variable light and high nitrate levels, with Phaeocystis antarctica blooms being linked additionally to high iron availability. Emerging results indicate that different clones of Phaeocystis have substantial genetic plasticity, which may explain its appearance in a variety of environments. Given the evidence of Phaeocystis appearing in new systems, this trend will likely continue in the near future.
    Repository-Name: EPIC Alfred Wegener Institut
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  • 59
    facet.materialart.
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 16(1), pp. 513-536, ISSN: 1941-1405
    Publikationsdatum: 2024-01-31
    Beschreibung: 〈jats:p〉 For decades, multiple-driver/stressor research has examined interactions among drivers that will undergo large changes in the future: temperature, pH, nutrients, oxygen, pathogens, and more. However, the most commonly used experimental designs—present-versus-future and ANOVA—fail to contribute to general understanding or predictive power. Linking experimental design to process-based mathematical models would help us predict how ecosystems will behave in novel environmental conditions. We review a range of experimental designs and assess the best experimental path toward a predictive ecology. Full factorial response surface, fractional factorial, quadratic response surface, custom, space-filling, and especially optimal and sequential/adaptive designs can help us achieve more valuable scientific goals. Experiments using these designs are challenging to perform with long-lived organisms or at the community and ecosystem levels. But they remain our most promising path toward linking experiments and theory in multiple-driver research and making accurate, useful predictions. 〈/jats:p〉
    Repository-Name: EPIC Alfred Wegener Institut
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  • 60
    facet.materialart.
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    Annual Reviews
    In:  EPIC3Annual Review of Marine Science, Annual Reviews, 15(1), pp. 509-538, ISSN: 1941-1405
    Publikationsdatum: 2024-05-10
    Beschreibung: The regular movements of waves and tides are obvious representations of the oceans’ rhythmicity. But the rhythms of marine life span across ecological niches and timescales, including short (in the range of hours) and long (in the range of days and months) periods. These rhythms regulate the physiology and behavior of individuals, as well as their interactions with each other and with the environment. This review highlights examples of rhythmicity in marine animals and algae that represent important groups of marine life across different habitats. The examples cover ecologically highly relevant species and a growing number of laboratory model systems that are used to disentangle key mechanistic principles. The review introduces fundamental concepts of chronobiology, such as the distinction between rhythmic and endogenous oscillator–driven processes. It also addresses the relevance of studying diverse rhythms and oscillators, as well as their interconnection, for making better predictions of how species will respond to environmental perturbations, including climate change. As the review aims to address scientists from the diverse fields of marine biology, ecology, and molecular chronobiology, all of which have their own scientific terms, we provide definitions of key terms throughout the article.
    Repository-Name: EPIC Alfred Wegener Institut
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  • 61
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 14 (1996), S. 301-331 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Precise regulation of major histocompatibility complex class II (MHC-II) gene expression plays a crucial role in the control of the immune response. A major breakthrough in the elucidation of the molecular mechanisms involved in MHC-II regulation has recently come from the study of patients that suffer from a primary immunodeficiency resulting from regulatory defects in MHC-II expression. A genetic complementation cloning approach has led to the isolation of CIITA and RFX5, two essential MHC-II gene transactivators. CIITA and RFX5 are mutated in these patients, and the wild-type genes are capable of correcting their defect in MHC-II expression. The identification of these regulatory factors has furthered our understanding of the molecular mechanisms that regulate MHC-II genes. CIITA was found to be a non-DNA binding transactivator that functions as a molecular switch controlling both constitutive and inducible MHC-II expression. The finding that RFX5 is a subunit of the nuclear RFX-complex has confirmed that a deficiency in the binding of this complex is indeed the molecular basis for MHC-II deficiency in the majority of patients. Furthermore, the study of RFX has demonstrated that MHC-II promoter activity is dependent on the binding of higher-order complexes that are formed by highly specific cooperative binding interactions between certain MHC-II promoter-binding proteins. Two of these proteins belong to families of which the other members, although capable of binding to the same DNA motifs, are probably not directly involved in the control of MHC-II expression. Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention.
    Materialart: Digitale Medien
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  • 62
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 14 (1996), S. 397-440 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNFalpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGFbeta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNFalpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNFalpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNFalpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNFalpha at its apex. This led to the hypothesis that TNFalpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNFalpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNFalpha antibody have shown marked clinical benefit, verifying the hypothesis that TNFalpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNFalpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.
    Materialart: Digitale Medien
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  • 63
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 14 (1996), S. 511-532 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract In contrast with the study of alphabeta T cells, that of gammadelta T cells is relatively recent and stems from the discovery of their rearranged genes, rather than from any knowledge of their biological function. Thus, experiments designed to characterize their specificity and function have drawn heavily on our knowledge of alphabeta T cells. During the past few years, many studies, especially with mice lacking either alphabeta or gammadelta T cells, have demonstrated that gammadelta T cells can contribute to immune competence, but they do so in a way that is distinct from alphabeta T cells. It is also evident that gammadelta T cells may not recognize antigen the same way as do alphabeta T cells. Analysis of three protein antigens-the murine MHC class II IEk, the nonclassical MHC T10/T22, and the Herpes virus glycoprotein gI-indicates that gammadelta T cell recognition does not require antigen processing and that the proteins are recognized directly. In all three cases, recognition by these T cell clones involves neither peptides bound to these proteins nor peptides derived from them. Moreover, a group of small phosphate-containing nonpeptide compounds derived from mycobacterial extracts has been found to stimulate a major population of human peripheral gammadelta T cells in a T cell receptor (TCR)-dependent manner. This indicates that gammadelta T cells can respond to ligands that are different from those of alphabeta T cells. Analysis of complementarity determining region (CDR3) length distributions of gamma and delta chains indicates that they are more similar to those of immunoglobulins than to TCR alpha and beta. This further supports the idea that gammadelta and alphabeta T cells recognize antigens differently and suggests that gammadelta T cells may be more like immunoglobulins in their recognition properties. gammadelta T cells share many cell surface proteins with alphabeta T cells and are able to secrete lymphokines and express cytolytic activities in response to antigenic stimulation. These, together with the results cited above, indicate that gammadelta T cells can mediate cellular immune functions without a requirement for antigen processing. Thus, pathogens, damaged tissues, or even B and T cells can be recognized directly, and cellular immune responses can be initiated without a requirement for antigen degradation or specialized antigen-presenting cells. This would give gammadelta T cells greater flexibility than the more classical type of alphabeta T cell-mediated cellular immunity.
    Materialart: Digitale Medien
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  • 64
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 14 (1996), S. 649-681 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The transcription factor NF-kappaB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-kappaB is through interactions with an inhibitor protein called IkappaB. Recent evidence confirms the existence of multiple forms of IkappaB that appear to regulate NF-kappaB by distinct mechanisms. NF-kappaB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-kappaB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IkappaB. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-kappaB. In the nucleus, NF-kappaB dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-kappaB is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-kappaB activation, excitement in NF-kappaB research has been generated by the first report of a crystal structure for one form of NF-kappaB, the first gene knockout studies for different forms of NF-kappaB and of IkappaB, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-kappaB.
    Materialart: Digitale Medien
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  • 65
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 93-124 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Naturally occurring genetic disorders of the immune system provide many models for the study of its development and function. In a way, their analysis complements the information provided by the generation of genetic defects in mice created using homologous recombination techniques. In this review, the recent findings made in three areas are focused upon deficiencies in T cell differentiation and in T lymphocyte activation, and on the control process of peripheral immune response.
    Materialart: Digitale Medien
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  • 66
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 203-234 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract This review deals with membrane Fc receptors (FcR) of the immunoglobulin superfamily. It is focused on the mechanisms by which FcR trigger and regulate biological responses of cells on which they are expressed. FcR deliver signals when they are aggregated at the cell surface. The aggregation of FcR having immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially src family tyrosine kinases and syk family tyrosine kinases that connect transduced signals to common activation pathways shared with other receptors. FcR with ITAMs elicit cell activation, endocytosis, and phagocytosis. The nature of responses depends primarily on the cell type. The aggregation of FcR without ITAM does not trigger cell activation. Most of these FcR internalize their ligands, which can be endocytosed, phagocytosed, or transcytosed. The fate of internalized receptor-ligand complexes depends on defined sequences in the intracytoplasmic domain of the receptors. The coaggregation of different FcR results in positive or negative cooperation. Some FcR without ITAM use FcR with ITAM as signal transduction subunits. The coaggregation of antigen receptors or of FcR having ITAMs with FcR having immunoreceptor tyrosine-based inhibition motifs (ITIMs) negatively regulates cell activation. FcR therefore appear as the subunits of multichain receptors whose constitution is not predetermined and which deliver adaptative messages as a function of the environment.
    Materialart: Digitale Medien
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  • 67
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 297-322 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract T helper lymphocytes can be divided into two distinct subsets of effector cells based on their functional capabilities and the profile of cytokines they produce. The Th1 subset of CD4+ T cells secretes cytokines usually associated with inflammation, such as IFN-gamma and TNF and induces cell-mediated immune responses. The Th2 subset produces cytokines such as IL-4 and IL-5 that help B cells to proliferate and differentiate and is associated with humoral-type immune responses. The selective differentiation of either subset is established during priming and can be significantly influenced by a variety of factors. One of these factors, the cytokine environment, has been put forward as the major variable influencing Th development and is already well reviewed by others. Instead, in the current review, we focus on some of the alternative approaches for skewing Th1/Th2 responses. Specifically, we discuss the effects on Th priming of (a) using altered peptide ligands as antigens, (b) varying the dose of antigen, and (c) altering costimulatory signals. The potential importance of each of these variables to influence immune responses to pathogens in vivo is discussed throughout.
    Materialart: Digitale Medien
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  • 68
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 405-431 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Epstein-Barr virus (EBV) provides one of the most informative systems with which to study cytotoxic T lymphocyte (CTL) responses in humans. The virus establishes a highly immunogenic growth-transforming infection of B lymphocytes, associated with the coordinate expression of six virus-coded nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, -LP) and two latent membrane proteins (LMPs 1 and 2). This elicits both primary and memory CT8+ CTL responses that are markedly skewed toward HLA allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins, with reactivities to other antigens being generally much less frequent. This heirarchy of immunodominance among the different latent proteins may at least partly reflect their differential accessibility to the HLA class I-processing pathway. Furthermore, CTLs to some of the immunodominant epitopes involve highly conserved T cell receptor (TCR) usage, a level of focusing which evidence suggests could have immunopathological consequences from cross-reactive recognition of other target structures. EBV is associated with a range of human tumors, and there is increasing interest in the possibility of targeting such malignancies using virus-specific CTLs. The dramatic reversal of EBV-driven lymphoproliferations in bone marrow transplant patients following CTL infusion demonstrates the potential of this approach, and here we discuss prospects for its extension to other EBV-positive tumors in which the immunodominant EBNA3A, 3B, 3C proteins are not expressed.
    Materialart: Digitale Medien
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  • 69
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 535-562 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract NK1 T cells are a specialized population of alpha/beta T cells that coexpress receptors of the NK lineage and have the unique potential to very rapidly secrete large amounts of cytokines, providing early help for effector cells and regulating the Th1 or Th2 differentiation of some immune responses. NK1 T cells express a restricted TCR repertoire made of an invariant TCR alpha chain, Valpha14-Jalpha281, associated with polyclonal Vbeta8, Vbeta7, and Vbeta2 TCR beta chains. NK1 T cells recognize the products of the conserved family of MHC class I-like CD1 genes, apparently in the absence of foreign antigens. Thus, this novel regulatory pathway, which straddles the innate and the adaptive immune systems, is unique in that its activation may not require associative recognition of antigen. Here, we review the specificity and function of mouse NK1 T cells, and we discuss the relationship of this lineage to mainstream T cells and NK cells.
    Materialart: Digitale Medien
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  • 70
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 15 (1997), S. 797-819 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Receptors for most interleukins and cytokines that regulate immune and hematopoietic systems belong to the class I cytokine receptor family. These molecules form multichain receptor complexes in order to exhibit high-affinity binding to, and mediate biological functions of, their respective cytokines. In most cases, these functional receptor complexes share common signal transducing receptor components that are also in the class I cytokine receptor family, i.e. gp130, common beta, and common gamma molecules. Interleukin-6 and related cytokines, interleukin-11, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, and cardiotrophin-1 are all pleiotropic and exhibit overlapping biological functions. Functional receptor complexes for this interleukin-6 family of cytokines share gp130 as a component critical for signal transduction. Unlike cytokines sharing common beta and common gamma chains that mainly function in hematopoietic and lymphoid cell systems, the interleukin-6 family of cytokines function extensively outside these systems as well, e.g. from the cardiovascular to the nervous system, owing to ubiquitously expressed gp130. Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. Although gp130 and its dimer partners possess no intrinsic tyrosine kinase domain, the dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors. This paper reviews recent progress in the study of the interleukin-6 family of cytokines and gp130.
    Materialart: Digitale Medien
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  • 71
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 1-25 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: At first one is very pleased at being invited to write a Prefatory Chapter, but as the delivery deadline draws closer one begins to think, "Oh my God! What on earth can I say that all but family members and few close friends will not find a great bore?" One solution is to write a scientific essay, but I concluded that that was a cop-out. I decided that perhaps the best tack to follow was to try to convey to the reader the personal characteristics I bring to my science and to other aspects of my professional career. The writing of this chapter has certainly convinced me that my particular background influenced what problems I chose to work on and how I approached their solution, but I hope that my results have a more ecumenical significance. There's been much written recently about how one's cultural background affects one's science, but I think that thesis can also be exaggerated. Science is a method of inquiry that by using certain guidelines permits rational individuals to observe Nature in a way that their findings will agree and have permanence. We shouldn't be diffident about defending that claim of objectivity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 72
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 111-135 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract CD40-CD154-mediated contact-dependent signals between B and T cells are required for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154 interactions are however also important in many other cell systems. CD40 is expressed by a large variety of cell types other than B cells, and these include dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in immune responses. Recently published studies indicate that CD40-CD154 interactions can influence T cell priming and T cell-mediated effector functions; they can also upregulate costimulatory molecules and activate macrophages, NK cells, and endothelia as well as participate in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. This review focuses on the role of the CD40-CD154 system in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 73
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 201-223 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Immunological memory can be defined as the faster and stronger response of an animal that follows reexposure to the same antigen. By this definition, it is an operational property of the whole animal or the immune system. Memory cells express a different pattern of cell surface markers, and they respond in several ways that are functionally different from those of naive cells. Murine memory cells are CD44 high and low in the expression of activation markers such as CD25 (IL-2R), whereas human memory cells are CD45RA-, CD45RO+. In contrast to naive cells, memory cells secrete a full range of T cell cytokines and can be polarized to secrete particular restricted patterns of secretion for both CD4 and CD8 T cells. The requirements for the activation of memory cells for proliferation and cytokine production are not quite as strict as those of naive cells, but costimulation in the broad sense is required for optimum responses and for responses to suboptimum antigen concentrations. It would appear that memory cells can persist in the absence of antigenic stimulation and persist as nondividing cells. Reencounter with the same antigen can expand the population to a new, stable, higher level and generate a separate population of CD44 high effectors that may be required for protection, while competition from other antigens can drive it down to a lower stable level. It is unclear how or where memory cells arise, but once generated they have different pathways of recirculation and homing.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 74
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 359-393 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract NK cells are regulated by opposing signals from receptors that activate and inhibit effector function. While positive stimulation may be initiated by an array of co-stimulatory receptors, specificity is provided by inhibitory signals transduced by receptors for MHC class I. Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules. A common pathway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these otherwise structurally diverse receptors. Upon ligand binding and activation, the inhibitory NK cell receptors become tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 and possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxicity and cytokine expression. Recent studies suggest these inhibitory NK cell receptors are members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS).
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 75
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 433-470 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract This review summarizes the clinical history and rationale for xenotransplantation; recent progress in understanding the physiologic, immunologic, and infectious obstacles to the procedure's success; and some of the strategies being pursued to overcome these obstacles. The problems of xenotransplantation are complex, and a combination of approaches is required. The earliest and most striking immunologic obstacle, that of hyperacute rejection, appears to be the closest to being solved. This phenomenon depends on the binding of natural antibody to the vascular endothelium, fixation of complement by that antibody, and finally, activation of the endothelium and initiation of coagulation. Therefore, these three pathways have been targeted as sites for intervention in the process. The mechanisms responsible for the next immunologic barrier, that of delayed xenograft/acute vascular rejection, remain to be fully elucidated. They probably also involve multiple pathways, including antibody and/or immune cell binding and endothelial cell activation. The final immunologic barrier, that of the cellular immune response, involves mechanisms that are similar to those involved in allograft rejection. However, the strength of the cellular immune response to xenografts is so great that it is unlikely to be controlled by the types of nonspecific immunosuppression used routinely to prevent allograft rejection. For this reason, it may be essential to induce specific immunologic unresponsiveness to at least some of the most antigenic xenogeneic molecules.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 76
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 16 (1998), S. 545-568 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Covalent attachment of activated complement C3 (C3d) to antigen links innate and adaptive immunity by targeting antigen to follicular dendritic cells (FDC) and B cells via specific receptors CD21 and CD35. Recent characterization of knockout mice deficient in complement components C3, C4, or the receptors CD21 and CD35 as well as biochemical studies of the CD21/CD19/Tapa-1 coreceptor on B cells have helped to elucidate the mechanism of complement regulation of both B-1 and B-2 lymphocytes. Interestingly, natural antibody of the adaptive immune system provides a major recognition role in activation of the complement system, which in turn enhances activation of antigen-specific B cells. Enhancement of the primary and secondary immune response to T-dependent antigens is mediated by coligation of the coreceptor and the B cell antigen receptor, which dramatically increases follicular retention and B cell survival within the germinal center. Most recent evidence suggests that complement also regulates elimination of self-reactive B cells, as breeding of mice that are deficient in C4 or CD21/CD35 with the lupus-prone strain of lpr mice demonstrates an exacerbation of disease due to an increase in autoantibodies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 77
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 1-17 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Work done in the late 1950s and in the 1960s revealed the role of the thymus in virus-induced leukemia in mice. Thymectomizing mice at birth to test whether the virus first multiplied in thymus tissue and then spread elsewhere ultimately led to the conclusion that the thymus was essential to the normal development of the immune system. Subsequent testing to try to understand how the thymus contributes to the pool of immunocompetent lymphocytes opened a new chapter in immunology and required a reappraisal of many immunological phenomena and an understanding of the molecular interactions that take place during cell-to-cell interactions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 78
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 19-49 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 alpha-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5' UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15Rbeta and gammac, subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15Ralpha. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 79
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 189-220 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Natural killer (NK) cells are populations of lymphocytes that can be activated to mediate significant levels of cytotoxic activity and produce high levels of certain cytokines and chemokines. NK cells respond to and are important in defense against a number of different infectious agents. The first indications for this function came from the observations that virus-induced interferons alpha/beta (IFN-alpha and -beta) are potent inducers of NK cell-mediated cytotoxicity, and that NK cells are important contributors to innate defense against viral infections. In addition to IFN-alpha/beta, a wide range of other innate cytokines can mediate biological functions regulating the NK cell responses of cytotoxicity, proliferation, and gamma interferon (IFN-gamma) production. Certain, but not all, viral infections induce interleukin 12 (IL-12) to elicit NK cell IFN-gamma production and antiviral mechanisms. However, high levels of IFN-alpha/beta appear to be unique and/or uniquely dominant in the context of viral infections and act to regulate other innate responses, including induction of NK cell proliferation in vivo and overall negative regulation of IL-12 production. A detailed picture is developing of particular innate cytokines activating NK cell responses and their consorted effects in providing unique endogenous milieus promoting downstream adaptive responses, most beneficial in defense against viral infections.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 80
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 331-367 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, LT-alpha, LT-beta, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor (CD120b), the lymphotoxin beta receptor (LTbetaR), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune response functions. Of these, the most thoroughly studied are cell death induction and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signaling by the TNF system and CD95. The downstream signaling molecules identified so far-caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-kappaB activation cascade-mediate the effects of other inducers as well. However, the molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 81
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 369-397 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of alphabeta T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR Valpha domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the Vbeta positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 555-592 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B cell antigen receptor (BCR). Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development. Combinations of intracellular signaling pathways downstream of these PTKs determine the quality and quantity of BCR signaling. For example, concerted actions of the PLC-gamma2 and PI3-K pathways are required for proper calcium responses. Similarly, the regulation of ERK and JNK responses involves both PLC-gamma2 and GTPases pathways. Since the immune response in vivo is regulated by alteration of these signaling outcomes, achieving a precise understanding of intracellular molecular events leading to B lymphocyte proliferation, deletion, anergy, receptor editing, and survival still remains a challenge for the future.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 83
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 593-623 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Phagocytosis of pathogens by macrophages initiates the innate immune response, which in turn orchestrates the adaptive response. In order to discriminate between infectious agents and self, macrophages have evolved a restricted number of phagocytic receptors, like the mannose receptor, that recognize conserved motifs on pathogens. Pathogens are also phagocytosed by complement receptors after relatively nonspecific opsonization with complement and by Fc receptors after specific opsonization with antibodies. All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle. However, important differences in the molecular mechanisms underlying phagocytosis by different receptors are now being appreciated. These include differences in the cytoskeletal elements that mediate ingestion, differences in vacuole maturation, and differences in inflammatory responses. Infectious agents, such as M. tuberculosis, Legionella pneumophila, and Salmonella typhimurium, enter macrophages via heterogeneous pathways and modify vacuolar maturation in a manner that favors their survival. Macrophages also play an important role in the recognition and clearance of apoptotic cells; a notable feature of this process is the absence of an inflammatory response.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 84
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 781-828 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The immune system relies on cell death to maintain lymphoid homeostasis and avoid disease. Recent evidence has indicated that the caspase family of cysteine proteases is a central effector in apoptotic cell death and is absolutely responsible for many of the morphological features of apoptosis. Cell death, however, can occur through caspase-independent and caspase-dependent pathways. In the case of cells that are irreversibly neglected or damaged, death occurs even in the absence of caspase activity. In contrast, healthy cells require caspase activation to undergo cell death induced by surface receptors. This review summarizes the current understanding of these two pathways of cell death in the immune system.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 85
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 17 (1999), S. 973-976 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 86
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 1-17 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The discovery that genes in the major histocompatibility complex (MHC) play an important role in the immune response depended on the chance interaction of several unrelated events. The first, and most important, was the decision by Michael Sela to synthesize a series of branched, multichain, synthetic polypeptides based on a backbone of poly-l-lysine. The prototype compound, (T,G)-A-L, was tipped with short random sequences of tyrosine and glutamic acid. This resulted in a restricted range of antigenic determinants composed of only two or three amino acids with a variable length-ideal for binding to the peptide binding groove of MHC class II molecules. The second was the decision by John Humphrey to immunize various strains of rabbits with this synthetic polypeptide. Two of these rabbit strains showed very large quantitative differences in antibody response to (T,G)-A-L. In transferring this system to inbred mouse strains, the third bit of good fortune was the availability at the National Institute of Medical Research, in Mill Hill (London), of the CBA (H2k) and C57 (H2b) strains. The H2b haplotype is the only one mediating a uniform high antibody response to (T,G)-A-L. The fourth critical ingredient was the availability of numerous congenic and H2 recombinant inbred strains of mice produced earlier by Snell, Stimpfling, Shreffler, and Klein. A search for congenic pairs of mice expressing the responder and nonresponder H2 haplotypes on the same background revealed that these strains responded as a function of their H2 haplotype, not of their inbred background. Extensive studies in a variety of inbred strains carrying recombinant H2 haplotypes, as well as a four-point linkage cross, mapped immune response to (T,G)A-L within the murine MHC, between the K and Ss loci. The demonstration that stimulation in the mixed lymphocyte reaction (MLR) mapped to the same region quickly led to attempts to produce antisera in congenic H2 recombinant strain combinations. These antisera identified I-region associated (Ia) antigens. Immunoprecipitation and blocking studies showed that the gene products controlling specific immune responses, the mixed lymphocyte reaction, and the structure of Ia antigens were one and the same-now designated as the I-A MHC class II molecules. These antisera and inbred strains enabled Unanue to demonstrate the peptide binding function of class II MHC molecules.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 165-184 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Ligation of the T cell antigen receptor (TCR) stimulates protein tyrosine kinases (PTKs), which regulate intracellular calcium and control the activity of protein kinase C (PKC) isozymes. PTKs activated by antigen receptors and costimulatory molecules also couple to phosphatidylinositol-3 kinase (PI3K) and control the activity of Ras- and Rho-family GTPases. T cell signal transduction is triggered physiologically by antigen in the context of antigen presenting cells (APC). The formation of stable and prolonged contacts between T cells and APCs is not neccessary to initiate T cell signaling but is required for effective T cell proliferation and differentiation. The stabilization of the T cell/ APC conjugate is regulated by intracellular signals induced by antigen receptors and costimulators. These coordinate the regulation of the actin and microtubule cytoskeleton and organize a specialized signaling zone that allows sustained TCR signaling.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 88
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 245-273 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell-mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell-based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 89
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 347-366 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Allergic diseases affect approximately one third of the general population. This class of disease, characterized by elevated serum IgE levels and hypersensitivity to normally innocuous antigen, can manifest in practically any mucosal tissue or as a systemic response. A few examples of serious allergic diseases include asthma, dermatitis, bee sting allergy, food allergy, conjunctivitis, and severe systemic anaphylaxis. Taken together, allergic diseases constitute one of the major problems of modern day medicine. A considerable portion of the healthcare budget is expended in the treatment of allergic disease, and morbidity rates of inner city asthmatics are rising steadily. Due to the enormity of the problem, there has been a worldwide effort to identify factors that contribute to the etiology of allergic diseases. Epidemiologic studies of multigeneration families and large numbers of twins clearly indicate a strong genetic component to atopic diseases. At least two independently segregating diseasesusceptibility genes are thought to come together with environmental factors to result in allergic inflammation in a particular tissue. On the basis of the strong genetic studies, multiple groups have attempted to identify disease-susceptibility genes via either a candidate gene approach or by genome-wide scans. Both of these approaches have implicated multiple regions in the human and mouse genomes, which are currently being evaluated as harboring putative atopy genes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 529-560 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The human thymus is a complex chimeric organ comprised of central (thymic epithelial space) and peripheral (perivascular space) components that functions well into adult life to produce naive T lymphocytes. Recent advances in identifying thymic emigrants and development of safe methods to study thymic function in vivo in adults have provided new opportunities to understand the role that the human thymus plays in immune reconstitution in aging, in bone marrow transplantation, and in HIV-1 infection. The emerging concept is that there are age-dependent contributions of thymic emigrants and proliferation of postthymic T cells to maintain the peripheral T cell pool and to contribute to T cell regeneration, with the thymus contributing more at younger ages and peripheral T cell expansion contributing more in older subjects. New studies have revealed a dynamic interplay between postnatal thymus output and peripheral T cell pool proliferation, which play important roles in determining the nature of immune reconstitution in congenital immunodeficiency diseases, in bone marrow transplantation, and in HIV-1 infection. In this paper, we review recent data on human postnatal thymus function that, taken together, support the notion that the human thymus is functional well into the sixth decade and plays a role throughout life to optimize human immune system function.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 91
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 709-737 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Antibodies can completely suppress or enhance the antibody response to their specific antigen by several hundredfold. Immunoglobulin M (IgM) enhances antibody responses via the complement system, and complement activation by IgM probably starts the chain of events leading to antibody responses to suboptimal antigen doses. IgG can enhance primary antibody responses in the absence of the complement system and seems to be dependent on Fc receptors for IgG (FcgammaRs). IgE enhances antibody responses via the low-affinity receptor for IgE (FcepsilonRII/CD23). The precise effector mechanisms that cause enhancement are not known, but direct B-cell signaling, antigen presentation, and increased follicular localization are all possibilities. IgG, IgE, and IgM may also suppress antibody responses when used in certain immunization regimes, and it seems reasonable that an important mechanism behind suppression is the masking of antigenic epitopes by antibodies. In addition, FcgammaRIIB, which contains a cytoplasmic inhibitory motif, acts as a negative regulator of antibody responses. This receptor, however, may prevent the antibody responses from exceeding a certain level rather than causing complete suppression.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 767-811 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Dendritic cells (DCs) are antigen-presenting cells with a unique ability to induce primary immune responses. DCs capture and transfer information from the outside world to the cells of the adaptive immune system. DCs are not only critical for the induction of primary immune responses, but may also be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response. Although our understanding of DC biology is still in its infancy, we are now beginning to use DC-based immunotherapy protocols to elicit immunity against cancer and infectious diseases.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 18 (2000), S. 927-974 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract The development and widespread use of vaccines against infectious agents have been a great triumph of medical science. One reason for the success of currently available vaccines is that they are capable of inducing long-lived antibody responses, which are the principal agents of immune protection against most viruses and bacteria. Despite these successes, vaccination against intracellular organisms that require cell-mediated immunity, such as the agents of tuberculosis, malaria, leishmaniasis, and human immunodeficiency virus infection, are either not available or not uniformly effective. Owing to the substantial morbidity and mortality associated with these diseases worldwide, an understanding of the mechanisms involved in generating long-lived cellular immune responses has tremendous practical importance. For these reasons, a new form of vaccination, using DNA that contains the gene for the antigen of interest, is under intensive investigation, because it can engender both humoral and cellular immune responses. This review focuses on the mechanisms by which DNA vaccines elicit immune responses. In addition, a list of potential applications in a variety of preclinical models is provided.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 19 (2001), S. 23-45 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Physical detection of antigen-specific CD4 T cells has revealed features of the in vivo immune response that were not appreciated from in vitro studies. In vivo, antigen is initially presented to naive CD4 T cells exclusively by dendritic cells within the T cell areas of secondary lymphoid tissues. Anatomic constraints make it likely that these dendritic cells acquire the antigen at the site where it enters the body. Inflammation enhances in vivo T cell activation by stimulating dendritic cells to migrate to the T cell areas and display stable peptide-MHC complexes and costimulatory ligands. Once stimulated by a dendritic cell, antigen-specific CD4 T cells produce IL-2 but proliferate in an IL-2-independent fashion. Inflammatory signals induce chemokine receptors on activated T cells that direct their migration into the B cell areas to interact with antigen-specific B cells. Most of the activated T cells then die within the lymphoid tissues. However, in the presence of inflammation, a population of memory T cells survives. This population is composed of two functional classes. One recirculates through nonlymphoid tissues and is capable of immediate effector lymphokine production. The other recirculates through lymph nodes and quickly acquires the capacity to produce effector lymphokines if stimulated. Therefore, antigenic stimulation in the presence of inflammation produces an increased number of specific T cells capable of producing effector lymphokines throughout the body.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 19 (2001), S. 163-196 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNFalpha, chemokines, and growth factors are expressed in diseased joints. The rationale that TNFalpha played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNFalpha antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNFalpha antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activcity of TNFalpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNFalpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center clinical trials of human TNFalpha inhibitors have demonstrated their consistent and remarkable efficacy in controlling signs and symptoms, with a favorable safety profile, in approximately two thirds of patients for up to 2 years, and their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Natural killer cells can discriminate between normal cells and cells that do not express adequate amounts of major histocompatibility complex (MHC) class I molecules. The discovery, both in mouse and in human, of MHC-specific inhibitory receptors clarified the molecular basis of this important NK cell function. However, the triggering receptors responsible for positive NK cell stimulation remained elusive until recently. Some of these receptors have now been identified in humans, thus shedding some light on the molecular mechanisms involved in NK cell activation during the process of natural cytotoxicity. Three novel, NK-specific, triggering surface molecules (NKp46, NKp30, and NKp44) have been identified. They represent the first members of a novel emerging group of receptors collectively termed natural cytotoxicity receptors (NCR). Monoclonal antibodies (mAbs) to NCR block to differing extents the NK-mediated lysis of various tumors. Moreover, lysis of certain tumors can be virtually abrogated by the simultaneous masking of the three NCRs. There is a coordinated surface expression of the three NCRs, their surface density varying in different individuals and also in the NK cells isolated from a given individual. A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various tumors. NKp46 is the only NCR involved in human NK-mediated killing of murine target cells. Accordingly, a homologue of NKp46 has been detected in mouse. Molecular cloning of NCR revealed novel members of the Ig superfamily displaying a low degree of similarity to each other and to known human molecules. NCRs are coupled to different signal transducing adaptor proteins, including CD3zeta, FcRIgamma, and KARAP/DAP12. Another triggering NK receptor is NKG2D. It appears to play either a complementary or a synergistic role with NCRs. Thus, the triggering of NK cells in the process of tumor cell lysis may often depend on the concerted action of NCR and NKG2D. In some instances, however, it may uniquely depend upon the activity of NCR or NKG2D only. Strict NKG2D-dependency can be appreciated using clones that, in spite of their NCRdull phenotype, efficiently lyse certain epithelial tumors or leukemic cell lines. Other triggering surface molecules including 2B4 and the novel NKp80 appear to function as coreceptors rather than as true receptors. Indeed, they can induce natural cytotoxicity only when co-engaged with a triggering receptor. While an altered expression or function of NCR or NKG2D is being explored as a possible cause of immunological disorders, 2B4 dysfunction has already been associated with a severe form of immunodeficiency. Indeed, in patients with the X-linked lymphoproliferative disease, the inability to control Epstein-Barr virus infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory instead of activating functions.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 19 (2001), S. 497-521 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract Elevation of intracellular free Ca2+ is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca2+ signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca2+ sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca2+ from intracellular stores, and by depleting the stores trigger prolonged Ca2+ influx through store-operated Ca2+ (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca2+ signal are shaped by several mechanisms, including K+ channels and membrane potential, slow modulation of the plasma membrane Ca2+-ATPase, and mitochondria that buffer Ca2+ and prevent the inactivation of CRAC channels. Ca2+ signals have a number of downstream targets occurring on multiple time scales. At short times, Ca2+ signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca2+ signals increase the efficiency and specificity of gene activation events. The complexity of Ca2+ signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 19 (2001), S. 595-621 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: Abstract B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5+ B cells. Finally, focusing on CD5+ cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline VH-VL combinations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 87-115 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
  • 100
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 1 (1983), S. 143-173 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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