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991.
Hangnoh Lee C Joel McManus Dong-Yeon Cho Matthew Eaton Fioranna Renda Maria Patrizia Somma Lucy Cherbas Gemma May Sara Powell Dayu Zhang Lijun Zhan Alissa Resch Justen Andrews Susan E Celniker Peter Cherbas Teresa M Przytycka Maurizio Gatti Brian Oliver Brenton Graveley David MacAlpine 《Genome biology》2014,15(8)
Background
Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at the organismal level, but are common in immortalized cell lines and tumors, where they may be an advantage to cells. In order to explore the biological consequences of copy number changes in the Drosophila genome, we resequenced the genomes of 19 tissue-culture cell lines and generated RNA-Seq profiles.Results
Our work revealed dramatic duplications and deletions in all cell lines. We found three lines of evidence indicating that copy number changes were due to selection during tissue culture. First, we found that copy numbers correlated to maintain stoichiometric balance in protein complexes and biochemical pathways, consistent with the gene balance hypothesis. Second, while most copy number changes were cell line-specific, we identified some copy number changes shared by many of the independent cell lines. These included dramatic recurrence of increased copy number of the PDGF/VEGF receptor, which is also over-expressed in many cancer cells, and of bantam, an anti-apoptosis miRNA. Third, even when copy number changes seemed distinct between lines, there was strong evidence that they supported a common phenotypic outcome. For example, we found that proto-oncogenes were over-represented in one cell line (S2-DRSC), whereas tumor suppressor genes were under-represented in another (Kc167).Conclusion
Our study illustrates how genome structure changes may contribute to selection of cell lines in vitro. This has implications for other cell-level natural selection progressions, including tumorigenesis.Electronic supplementary material
The online version of this article (doi:10.1186/gb-2014-15-8-r70) contains supplementary material, which is available to authorized users. 相似文献992.
Kimberly R. Andrews Emily L. Norton Iria Fernandez‐Silva Elan Portner Erica Goetze 《Molecular ecology》2014,23(22):5462-5479
Zooplanktonic taxa have a greater number of distinct populations and species than might be predicted based on their large population sizes and open‐ocean habitat, which lacks obvious physical barriers to dispersal and gene flow. To gain insight into the evolutionary mechanisms driving genetic diversification in zooplankton, we developed eight microsatellite markers to examine the population structure of an abundant, globally distributed mesopelagic copepod, Haloptilus longicornis, at 18 sample sites across the Atlantic and Pacific Oceans (n = 761). When comparing our microsatellite results with those of a prior study that used a mtDNA marker (mtCOII, n = 1059, 43 sample sites), we unexpectedly found evidence for the presence of a cryptic species pair. These species were globally distributed and apparently sympatric, and were separated by relatively weak genetic divergence (reciprocally monophyletic mtCOII lineages 1.6% divergent; microsatellite FST ranging from 0.28 to 0.88 across loci, P < 0.00001). Using both mtDNA and microsatellite data for the most common of the two species (n = 669 for microsatellites, n = 572 for mtDNA), we also found evidence for allopatric barriers to gene flow within species, with distinct populations separated by continental landmasses and equatorial waters in both the Atlantic and Pacific Ocean basins. Our study shows that oceanic barriers to gene flow can act as a mechanism promoting allopatric diversification in holoplanktonic taxa, despite the high potential dispersal abilities and pelagic habitat for these species. 相似文献
993.
David J. D. Earn Paul W. Andrews Benjamin M. Bolker 《Proceedings. Biological sciences / The Royal Society》2014,281(1778)
Fever is commonly attenuated with antipyretic medication as a means to treat unpleasant symptoms of infectious diseases. We highlight a potentially important negative effect of fever suppression that becomes evident at the population level: reducing fever may increase transmission of associated infections. A higher transmission rate implies that a larger proportion of the population will be infected, so widespread antipyretic drug use is likely to lead to more illness and death than would be expected in a population that was not exposed to antipyretic pharmacotherapies. We assembled the published data available for estimating the magnitudes of these individual effects for seasonal influenza. While the data are incomplete and heterogeneous, they suggest that, overall, fever suppression increases the expected number of influenza cases and deaths in the US: for pandemic influenza with reproduction number , the estimated increase is 1% (95% CI: 0.0–2.7%), whereas for seasonal influenza with , the estimated increase is 5% (95% CI: 0.2–12.1%). 相似文献
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996.
Platelet physiology: in cold blood 总被引:6,自引:0,他引:6
One of the impediments precluding long-term storage of platelets for blood transfusion is that refrigerated platelets are rapidly cleared from the circulation upon transfusion. New evidence suggests that this clearance is mediated in the liver by the Mac-1 integrin on Kupffer cells recognizing clustered GPIb receptor on platelets, leading to platelet phagocytosis. 相似文献
997.
Andrews NC 《Current opinion in chemical biology》2002,6(2):181-186
Iron and copper are essential nutrients that must be meticulously regulated to exploit their usefulness in biological reactions while protecting against their tendency to promote formation of toxic free-radicals. This review summarizes recently described steps in the transport of these metals, and explores how defects in these steps lead to human diseases including hemochromatosis, Menkes disease and Wilson disease. 相似文献
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999.
Fujiao Lv Fei Qi Zhi Zhang Maorong Wen Justin Kale Alessandro Piai Lingyu Du Shuqing Wang Liujuan Zhou Yaqing Yang Bin Wu Zhijun Liu Juan del Rosario Justin Pogmore James J Chou David W Andrews Jialing Lin Bo OuYang 《The EMBO journal》2021,40(14)
Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high‐resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure‐guided mutations demonstrate the importance of both types of protein–lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria. 相似文献
1000.