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  • Articles  (79)
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  • American Association for the Advancement of Science (AAAS)  (79)
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  • 1
    Publication Date: 2011-11-15
    Description: With its high-energy phosphate bonds, adenosine triphosphate (ATP) is the main intracellular energy carrier. It also functions in most signaling pathways, as a phosphate donor or a precursor for cyclic adenosine monophosphate. We show here that inositol pyrophosphates participate in the control of intracellular ATP concentration. Yeasts devoid of inositol pyrophosphates have dysfunctional mitochondria but, paradoxically, contain four times as much ATP because of increased glycolysis. We demonstrate that inositol pyrophosphates control the activity of the major glycolytic transcription factor GCR1. Thus, inositol pyrophosphates regulate ATP concentration by altering the glycolytic/mitochondrial metabolic ratio. Metabolic reprogramming through inositol pyrophosphates is an evolutionary conserved mechanism that is also preserved in mammalian systems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Szijgyarto, Zsolt -- Garedew, Assegid -- Azevedo, Cristina -- Saiardi, Adolfo -- G1001704/Medical Research Council/United Kingdom -- MC_U122680443/Medical Research Council/United Kingdom -- PG/10/72/28449/British Heart Foundation/United Kingdom -- New York, N.Y. -- Science. 2011 Nov 11;334(6057):802-5. doi: 10.1126/science.1211908.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology Unit, Medical Research Council Laboratory for Molecular Cell Biology, and Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22076377" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Monophosphate/metabolism ; Adenosine Triphosphate/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; *Energy Metabolism ; Gene Expression Regulation, Fungal ; Glucose/metabolism ; Glycolysis/genetics ; Inositol Phosphates/*metabolism ; Mitochondria/metabolism ; Mutation ; NAD/metabolism ; Oxidation-Reduction ; Oxidative Phosphorylation ; Oxygen Consumption ; Phosphorylation ; Recombinant Fusion Proteins/metabolism ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Transcription Factors/chemistry/genetics/*metabolism
    Print ISSN: 0036-8075
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  • 2
    Publication Date: 2011-03-26
    Description: Pervasive transcription of eukaryotic genomes generates a plethora of noncoding RNAs. In fission yeast, the heterochromatin factor Clr4/Suv39 methyltransferase facilitates RNA interference (RNAi)-mediated processing of centromeric transcripts into small interfering RNAs (siRNAs). Clr4 also mediates degradation of antisense RNAs at euchromatic loci, but the underlying mechanism has remained elusive. We show that Clr4 and the RNAi effector RITS (RNA-induced transcriptional silencing) interact with Mlo3, a protein related to mRNA quality control and export factors. Loss of Clr4 impairs RITS interaction with Mlo3, which is required for centromeric siRNA production and antisense suppression. Mlo3 also interacts with the RNA surveillance factor TRAMP, which suppresses antisense RNAs targeted by Clr4 and RNAi. These findings link Clr4 to RNA quality control machinery and suggest a pathway for processing potentially deleterious RNAs through the coordinated actions of RNAi and other RNA processing activities.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ke -- Fischer, Tamas -- Porter, Rebecca L -- Dhakshnamoorthy, Jothy -- Zofall, Martin -- Zhou, Ming -- Veenstra, Timothy -- Grewal, Shiv I S -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 25;331(6024):1624-7. doi: 10.1126/science.1198712.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biochemistry and Molecular Biology, National Cancer Institute/NIH, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21436456" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Cycle Proteins/genetics/*metabolism ; Centromere/metabolism ; Euchromatin/metabolism ; Histones/metabolism ; Methylation ; Methyltransferases/genetics/*metabolism ; Mutation ; *RNA Interference ; RNA Processing, Post-Transcriptional ; RNA, Antisense/*metabolism ; RNA, Fungal/*metabolism ; RNA-Binding Proteins/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces/*genetics/*metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minke, Baruch -- Peters, Maximilian -- New York, N.Y. -- Science. 2011 Mar 11;331(6022):1272-3. doi: 10.1126/science.1203482.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Neurobiology, The Institute of Medical Research Israel-Canada (IMRIC), The Hebrew University, Jerusalem, Israel. baruchm@ekmd.huji.ac.il〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21393531" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila Proteins/genetics/metabolism/*physiology ; Drosophila melanogaster/genetics/*physiology ; Larva/physiology ; Light ; Mutation ; Photoreceptor Cells, Invertebrate/physiology ; Rhodopsin/chemistry/genetics/*physiology ; TRPC Cation Channels/metabolism ; Temperature ; *Thermosensing
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elsasser, Simon J -- Allis, C David -- Lewis, Peter W -- New York, N.Y. -- Science. 2011 Mar 4;331(6021):1145-6. doi: 10.1126/science.1203280.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21385704" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Chromatin/metabolism ; Chromatin Assembly and Disassembly/genetics ; DNA Helicases/*genetics/metabolism ; *Epigenesis, Genetic ; *Genes, Tumor Suppressor ; Histones/metabolism ; Humans ; Mutation ; Neuroendocrine Tumors/*genetics/metabolism ; Nuclear Proteins/*genetics/metabolism ; Nucleosomes/metabolism ; Pancreatic Neoplasms/*genetics/metabolism ; Proto-Oncogene Proteins/*genetics/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-03-12
    Description: Partitioning of chromatids during mitosis requires that chromosome compaction and spindle length scale appropriately with each other. However, it is not clear whether chromosome condensation and spindle elongation are linked. Here, we find that yeast cells could cope with a 45% increase in the length of their longest chromosome arm by increasing its condensation. The spindle midzone, aurora/Ipl1 activity, and Ser10 of histone H3 mediated this response. Thus, the anaphase spindle may function as a ruler to adapt the condensation of chromatids, promoting their segregation regardless of chromosome or spindle length.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neurohr, Gabriel -- Naegeli, Andreas -- Titos, Iris -- Theler, Dominik -- Greber, Basil -- Diez, Javier -- Gabaldon, Toni -- Mendoza, Manuel -- Barral, Yves -- New York, N.Y. -- Science. 2011 Apr 22;332(6028):465-8. doi: 10.1126/science.1201578. Epub 2011 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG), Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21393511" target="_blank"〉PubMed〈/a〉
    Keywords: Aldose-Ketose Isomerases/genetics ; *Anaphase ; Aurora Kinases ; Chromosome Segregation ; Chromosomes, Fungal/genetics/*physiology ; Histones/metabolism ; Intracellular Signaling Peptides and Proteins/genetics/metabolism ; Microtubule-Associated Proteins/genetics/metabolism ; Mutation ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Saccharomyces cerevisiae/genetics/*physiology ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Spindle Apparatus/*physiology/*ultrastructure
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2011-05-14
    Description: We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164876/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fleishman, Sarel J -- Whitehead, Timothy A -- Ekiert, Damian C -- Dreyfus, Cyrille -- Corn, Jacob E -- Strauch, Eva-Maria -- Wilson, Ian A -- Baker, David -- AI057141/AI/NIAID NIH HHS/ -- AI058113/AI/NIAID NIH HHS/ -- GM080209/GM/NIGMS NIH HHS/ -- P01 AI058113/AI/NIAID NIH HHS/ -- P01 AI058113-07/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 May 13;332(6031):816-21. doi: 10.1126/science.1202617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21566186" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Binding Sites ; Computational Biology ; *Computer Simulation ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/*metabolism ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Hydrophobic and Hydrophilic Interactions ; *Models, Molecular ; Molecular Sequence Data ; Mutation ; Peptide Library ; Protein Binding ; Protein Conformation ; *Protein Engineering ; Protein Interaction Domains and Motifs ; Protein Structure, Secondary ; Proteins/*chemistry/genetics/*metabolism ; Software
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-08-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carroll, Sean B -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1100-1. doi: 10.1126/science.1211025.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Laboratory of Molecular Biology, University of Wisconsin-Madison, 201 Bock Laboratories, Madison, WI 53706, USA. sbcarrol@facstaff.wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21868661" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Animals ; *Biological Evolution ; Butterflies/anatomy & histology/*genetics ; *Genes, Insect ; Genetic Variation ; Mutation ; Phenotype ; Pigmentation/*genetics ; Regulatory Sequences, Nucleic Acid ; Selection, Genetic ; Wings, Animal/*anatomy & histology
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  • 8
    Publication Date: 2011-03-10
    Description: Light-responsive neural activity in central brain neurons is generally conveyed through opsin-based signaling from external photoreceptors. Large lateral ventral arousal neurons (lLNvs) in Drosophila melanogaster increase action potential firing within seconds in response to light in the absence of all opsin-based photoreceptors. Light-evoked changes in membrane resting potential occur in about 100 milliseconds. The light response is selective for blue wavelengths corresponding to the spectral sensitivity of CRYPTOCHROME (CRY). cry-null lines are light-unresponsive, but restored CRY expression in the lLNv rescues responsiveness. Furthermore, expression of CRY in neurons that are normally unresponsive to light confers responsiveness. The CRY-mediated light response requires a flavin redox-based mechanism and depends on potassium channel conductance, but is independent of the classical circadian CRY-TIMELESS interaction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418525/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418525/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fogle, Keri J -- Parson, Kelly G -- Dahm, Nicole A -- Holmes, Todd C -- NS046750/NS/NINDS NIH HHS/ -- R01 GM102965/GM/NIGMS NIH HHS/ -- R01 NS046750/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2011 Mar 18;331(6023):1409-13. doi: 10.1126/science.1199702. Epub 2011 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology and Biophysics, University of California-Irvine, Irvine, CA 92697, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21385718" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; *Circadian Clocks ; Circadian Rhythm ; Compound Eye, Arthropod/physiology ; Cryptochromes/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*physiology ; Eye Proteins/genetics/*metabolism ; Flavins/metabolism ; Genes, Insect ; *Light ; Mutation ; Neurons/physiology ; Oxidation-Reduction ; Patch-Clamp Techniques ; Photoreceptor Cells, Invertebrate/metabolism
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2011-09-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Normile, Dennis -- New York, N.Y. -- Science. 2011 Sep 9;333(6048):1369. doi: 10.1126/science.333.6048.1369.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21903787" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds ; Disease Outbreaks/statistics & numerical data/veterinary ; Humans ; *Influenza A Virus, H5N1 Subtype/genetics/immunology ; Influenza Vaccines ; Influenza in Birds/*epidemiology/prevention & control/virology ; Influenza, Human/*epidemiology ; Mutation ; Poultry
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2011-06-28
    Description: Centrosomes organize the bipolar mitotic spindle, and centrosomal defects cause chromosome instability. Protein phosphorylation modulates centrosome function, and we provide a comprehensive map of phosphorylation on intact yeast centrosomes (18 proteins). Mass spectrometry was used to identify 297 phosphorylation sites on centrosomes from different cell cycle stages. We observed different modes of phosphoregulation via specific protein kinases, phosphorylation site clustering, and conserved phosphorylated residues. Mutating all eight cyclin-dependent kinase (Cdk)-directed sites within the core component, Spc42, resulted in lethality and reduced centrosomal assembly. Alternatively, mutation of one conserved Cdk site within gamma-tubulin (Tub4-S360D) caused mitotic delay and aberrant anaphase spindle elongation. Our work establishes the extent and complexity of this prominent posttranslational modification in centrosome biology and provides specific examples of phosphorylation control in centrosome function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825980/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825980/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keck, Jamie M -- Jones, Michele H -- Wong, Catherine C L -- Binkley, Jonathan -- Chen, Daici -- Jaspersen, Sue L -- Holinger, Eric P -- Xu, Tao -- Niepel, Mario -- Rout, Michael P -- Vogel, Jackie -- Sidow, Arend -- Yates, John R 3rd -- Winey, Mark -- F32 GM086038/GM/NIGMS NIH HHS/ -- GM51312/GM/NIGMS NIH HHS/ -- MOP-64404/Canadian Institutes of Health Research/Canada -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 GM051312/GM/NIGMS NIH HHS/ -- R01 GM051312-16/GM/NIGMS NIH HHS/ -- R01 GM051312-16S1/GM/NIGMS NIH HHS/ -- R01 GM062427/GM/NIGMS NIH HHS/ -- R01 HG003039/HG/NHGRI NIH HHS/ -- T32 GM008759/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Jun 24;332(6037):1557-61. doi: 10.1126/science.1205193.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21700874" target="_blank"〉PubMed〈/a〉
    Keywords: Binding Sites ; CDC2 Protein Kinase/metabolism ; *Cell Cycle ; Centrosome/*metabolism/ultrastructure ; Cytoskeletal Proteins/genetics/metabolism ; Fungal Proteins/chemistry/metabolism ; Fungi/metabolism ; G1 Phase ; Mitosis ; Mutation ; Phosphoproteins/genetics/metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; Proteome/*metabolism ; Saccharomyces cerevisiae/cytology/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Spindle Apparatus/metabolism/ultrastructure ; Tubulin/chemistry/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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