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81.
Jäger S Cimermancic P Gulbahce N Johnson JR McGovern KE Clarke SC Shales M Mercenne G Pache L Li K Hernandez H Jang GM Roth SL Akiva E Marlett J Stephens M D'Orso I Fernandes J Fahey M Mahon C O'Donoghue AJ Todorovic A Morris JH Maltby DA Alber T Cagney G Bushman FD Young JA Chanda SK Sundquist WI Kortemme T Hernandez RD Craik CS Burlingame A Sali A Frankel AD Krogan NJ 《Nature》2012,481(7381):365-370
Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ~40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection. 相似文献
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Mackay TF Richards S Stone EA Barbadilla A Ayroles JF Zhu D Casillas S Han Y Magwire MM Cridland JM Richardson MF Anholt RR Barrón M Bess C Blankenburg KP Carbone MA Castellano D Chaboub L Duncan L Harris Z Javaid M Jayaseelan JC Jhangiani SN Jordan KW Lara F Lawrence F Lee SL Librado P Linheiro RS Lyman RF Mackey AJ Munidasa M Muzny DM Nazareth L Newsham I Perales L Pu LL Qu C Ràmia M Reid JG Rollmann SM Rozas J Saada N Turlapati L Worley KC Wu YQ Yamamoto A Zhu Y Bergman CM Thornton KR 《Nature》2012,482(7384):173-178
A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics. 相似文献
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Mutations in NOTCH1 cause aortic valve disease 总被引:2,自引:0,他引:2
Garg V Muth AN Ransom JF Schluterman MK Barnes R King IN Grossfeld PD Srivastava D 《Nature》2005,437(7056):270-274
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Human cytomegalovirus (HCMV) is a widespread opportunistic herpesvirus that causes severe and fatal diseases in immune-compromised individuals, including organ transplant recipients and individuals with AIDS. It is also a leading cause of virus-associated birth defects and is associated with atherosclerosis and coronary restenosis. HCMV initiates infection and intracellular signalling by binding to its cognate cellular receptors and by activating several signalling pathways including those mediated by mitogen-activated protein kinase, phosphatidylinositol-3-OH kinase, interferons, and G proteins. But a cellular receptor responsible for viral entry and HCMV-induced signalling has yet to be identified. Here we show that HCMV infects cells by interacting with epidermal growth factor receptor (EGFR) and inducing signalling. Transfecting EGFR-negative cells with an EGFR complementary DNA renders non-susceptible cells susceptible to HCMV. Ligand displacement and crosslinking analyses show that HCMV interacts with EGFR through gB, its principal envelope glycoprotein. gB preferentially binds EGFR and EGFR-ErbB3 oligomeric molecules in Chinese hamster ovary cells transfected with erbB family cDNAs. Taken together, these data indicate that EGFR is a necessary component for HCMV-triggered signalling and viral entry. 相似文献