全文获取类型
收费全文 | 5188篇 |
免费 | 549篇 |
国内免费 | 3篇 |
专业分类
5740篇 |
出版年
2022年 | 35篇 |
2021年 | 87篇 |
2020年 | 53篇 |
2019年 | 55篇 |
2018年 | 71篇 |
2017年 | 68篇 |
2016年 | 112篇 |
2015年 | 186篇 |
2014年 | 205篇 |
2013年 | 285篇 |
2012年 | 302篇 |
2011年 | 310篇 |
2010年 | 169篇 |
2009年 | 157篇 |
2008年 | 257篇 |
2007年 | 225篇 |
2006年 | 228篇 |
2005年 | 223篇 |
2004年 | 189篇 |
2003年 | 164篇 |
2002年 | 162篇 |
2001年 | 138篇 |
2000年 | 121篇 |
1999年 | 108篇 |
1998年 | 56篇 |
1997年 | 55篇 |
1996年 | 58篇 |
1995年 | 51篇 |
1994年 | 41篇 |
1993年 | 49篇 |
1992年 | 79篇 |
1991年 | 85篇 |
1990年 | 83篇 |
1989年 | 65篇 |
1988年 | 55篇 |
1987年 | 82篇 |
1986年 | 57篇 |
1985年 | 67篇 |
1984年 | 63篇 |
1983年 | 70篇 |
1982年 | 50篇 |
1981年 | 45篇 |
1980年 | 32篇 |
1979年 | 56篇 |
1978年 | 46篇 |
1977年 | 46篇 |
1976年 | 44篇 |
1974年 | 48篇 |
1972年 | 36篇 |
1967年 | 29篇 |
排序方式: 共有5740条查询结果,搜索用时 15 毫秒
901.
902.
Giménez-Abián JF Sumara I Hirota T Hauf S Gerlich D de la Torre C Ellenberg J Peters JM 《Current biology : CB》2004,14(13):1187-1193
Sister chromatid separation in anaphase depends on the removal of cohesin complexes from chromosomes. In vertebrates, the bulk of cohesin is already removed from chromosome arms during prophase and prometaphase, whereas cohesin remains at centromeres until metaphase, when cohesin is cleaved by the protease separase. In unperturbed mitoses, arm cohesion nevertheless persists throughout metaphase and is principally sufficient to maintain sister chromatid cohesion. How arm cohesion is maintained until metaphase is unknown. Here we show that small amounts of cohesin can be detected in the interchromatid region of metaphase chromosome arms. If prometaphase is prolonged by treatment of cells with microtubule poisons, these cohesin complexes dissociate from chromosome arms, and arm cohesion is dissolved. If cohesin dissociation in prometaphase-arrested cells is prevented by depletion of Plk1 or inhibition of Aurora B, arm cohesion is maintained. These observations imply that, in unperturbed mitoses, small amounts of cohesin maintain arm cohesion until metaphase. When cells lacking Plk1 and Aurora B activity enter anaphase, chromatids lose cohesin. This loss is prevented by proteasome inhibitors, implying that it depends on separase activation. Separase may therefore be able to cleave cohesin at centromeres and on chromosome arms. 相似文献
903.
Sequence-specific 1H-n.m.r. assignments and peptide backbone conformation in rat epidermal growth factor. 总被引:1,自引:0,他引:1 下载免费PDF全文
The solution conformation of rat epidermal growth factor (EGF) has been investigated by proton n.m.r. techniques. Two-dimensional proton n.m.r. experiments have allowed sequential resonance assignments to be made for most protons. On the basis of these assignments, two regions of anti-parallel beta-sheet structure have been derived from the n.m.r. data. A beta-sheet segment running from about V19 to V23 (capital letters refer to amino acids in the single-letter notation) is folded onto a beta-sheet segment running from R28 to N32 and joined by a chain reversal from E24 to D27. A second region involves a beta-turn from V34 to Y37, which starts a short beta-sheet up to G39, followed by a chain reversal up to Q43, which leads to folding of the C-terminal beta-sheet segment, i.e. H44-R45, running antiparallel to the short Y37 beta-sheet segment. The N-terminal segment up to G18 exists in a multiple bend conformation and is folded on to the V29-V23/R28-N32 beta-sheet such that Y10, Y13, Y22 and Y29 are proximal to each other. Structural comparison of rat, murine and human EGFs indicates a number of highly conserved structural features common to at least these species of EGF. 相似文献
904.
Magni Olsen Kyrkjeeide Kristian Hassel Kjell Ivar Flatberg A. Jonathan Shaw Narjes Yousefi Hans K. Sten?ien 《PloS one》2016,11(2)
Spore-producing organisms have small dispersal units enabling them to become widespread across continents. However, barriers to gene flow and cryptic speciation may exist. The common, haploid peatmoss Sphagnum magellanicum occurs in both the Northern and Southern hemisphere, and is commonly used as a model in studies of peatland ecology and peatmoss physiology. Even though it will likely act as a rich source in functional genomics studies in years to come, surprisingly little is known about levels of genetic variability and structuring in this species. Here, we assess for the first time how genetic variation in S. magellanicum is spatially structured across its full distribution range (Northern Hemisphere and South America). The morphologically similar species S. alaskense was included for comparison. In total, 195 plants were genotyped at 15 microsatellite loci. Sequences from two plastid loci (trnG and trnL) were obtained from 30 samples. Our results show that S. alaskense and almost all plants of S. magellanicum in the northern Pacific area are diploids and share the same gene pool. Haploid plants occur in South America, Europe, eastern North America, western North America, and southern Asia, and five genetically differentiated groups with different distribution ranges were found. Our results indicate that S. magellanicum consists of several distinct genetic groups, seemingly with little or no gene flow among them. Noteworthy, the geographical separation of diploids and haploids is strikingly similar to patterns found within other haploid Sphagnum species spanning the Northern Hemisphere. Our results confirm a genetic division between the Beringian and the Atlantic that seems to be a general pattern in Sphagnum taxa. The pattern of strong genetic population structuring throughout the distribution range of morphologically similar plants need to be considered in future functional genomic studies of S. magellanicum. 相似文献
905.
Andrey A. Rosenkranz Sergey V. Yachmenev David A. Jans Natalya V. Serebryakova Vitaly I. Murav''ev Reiner Peters Alexander S. Sobolev 《Experimental cell research》1992,199(2):323-329
A soluble construct consisting of a plasmid carrying the gene of the SV40 large T-antigen and an insulin-poly-L-lysine conjugate is able to selectively transfect PLC/PRF/5 human hepatoma cells which possess insulin receptors. Transfection can be efficiently competed by excess free insulin. To examine intracellular transport of the construct, it was fluorescently labeled and its accumulation on and in cells visualized by video-enhanced microscopy and quantitative confocal laser scanning microscopy. After 2 h at 37 degrees C, the labeled construct was found predominantly in intracellular acidic compartments, with a substantial portion of fluorescence localized both near and in the cell nucleus. Binding, endocytosis, and nuclear localization of the labeled conjugate could all be competed by excess free insulin, thus indicating that entry of the conjugate into cells was specifically mediated by the insulin receptor. 相似文献
906.
Angelika B?ttger Andrew C. Doxey Michael W. Hess Kristian Pfaller Willi Salvenmoser Rainer Deutzmann Andreas Geissner Barbara Pauly Johannes Altst?tter Sandra Münder Astrid Heim Hans-Joachim Gabius Brendan J. McConkey Charles N. David 《PloS one》2012,7(12)
The single-cell layered ectoderm of the fresh water polyp Hydra fulfills the function of an epidermis by protecting the animals from the surrounding medium. Its outer surface is covered by a fibrous structure termed the cuticle layer, with similarity to the extracellular surface coats of mammalian epithelia. In this paper we have identified molecular components of the cuticle. We show that its outermost layer contains glycoproteins and glycosaminoglycans and we have identified chondroitin and chondroitin-6-sulfate chains. In a search for proteins that could be involved in organising this structure we found PPOD proteins and several members of a protein family containing only SWT (sweet tooth) domains. Structural analyses indicate that PPODs consist of two tandem β-trefoil domains with similarity to carbohydrate-binding sites found in lectins. Experimental evidence confirmed that PPODs can bind sulfated glycans and are secreted into the cuticle layer from granules localized under the apical surface of the ectodermal epithelial cells. PPODs are taxon-specific proteins which appear to have entered the Hydra genome by horizontal gene transfer from bacteria. Their acquisition at the time Hydra evolved from a marine ancestor may have been critical for the transition to the freshwater environment. 相似文献
907.
908.
MF Hughes O Saarela J Stritzke F Kee K Silander N Klopp J Kontto J Karvanen C Willenborg V Salomaa J Virtamo P Amouyel D Arveiler J Ferrières PG Wiklund J Baumert B Thorand P Diemert DA Trégouët C Hengstenberg A Peters A Evans W Koenig J Erdmann NJ Samani K Kuulasmaa H Schunkert 《PloS one》2012,7(7):e40922
Background
More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.Methods
Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5–18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.Results
Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50–59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.Conclusions
Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men. 相似文献909.
Mapping of the structural gene for S-adenosyl homocysteine hydrolase to mouse Chromosome 2, and related sequences to Chromosomes 8 and X 总被引:1,自引:0,他引:1
Alison Pilz Paul Le Tissier Heather Moseley Jo Peters Cathy Abbott 《Mammalian genome》1992,3(11):633-636
Comparative mapping studies in human and mouse have shown that, to date, human Chromosome (Chr) 20 is completely syntenic with distal mouse Chr 2. The structural locus for S-adenosyl-l-homocysteine hydrolase (EC 3.3.1.1) in human, AHCY, maps to 20 qterq13.1, and we report here that the homologous locus in the mouse, Ahcy, maps to distal mouse Chr 2 with gene order Pcna-Ahcy-Ada. Analysis of 123 progeny of an interspecific backcross between a laboratory stock, AN, and Mus spretus using a rat cDNA probe revealed the presence of at least two other Ahcy-related sequences segregating independently in the mouse genome. One, Ahcy-rs1, was mapped to Chr 8 in the BXH recombinant inbred strains, and the other, Ahcy-rs2, shows a pattern of inheritance consistent with X-linkage. 相似文献
910.
R A Jackson P M Blix J A Matthews N Peters T R Pilkington A H Rubenstein J D Nabarro 《Hormones et métabolisme》1983,15(12):585-588
Forearm glucose uptake (FGU) was studied during 100 g oral glucose tolerance tests (GTT) in nonobese, nondiabetic men who had suffered a myocardial infarction (MI) at or before the age of 40, and the results compared with the response in age-matched normal men. In the MI group the rise in both glucose and insulin concentrations after glucose loading was similar to that in normal subjects, although in the former, peak levels tended to be slightly higher. Concomitant FGU, however, was significantly greater in the MI group than in control subjects in the period 0-90 min and in the test as a whole (0-180 min). The results show that at least in some nondiabetics suffering MI at an early age hyperinsulinism is not a feature and peripheral tissue sensitivity is increased. 相似文献