全文获取类型
收费全文 | 428551篇 |
免费 | 48324篇 |
国内免费 | 163篇 |
出版年
2018年 | 3936篇 |
2016年 | 5358篇 |
2015年 | 7038篇 |
2014年 | 8302篇 |
2013年 | 11436篇 |
2012年 | 13039篇 |
2011年 | 13471篇 |
2010年 | 9232篇 |
2009年 | 8572篇 |
2008年 | 12318篇 |
2007年 | 12882篇 |
2006年 | 12018篇 |
2005年 | 11515篇 |
2004年 | 11547篇 |
2003年 | 10849篇 |
2002年 | 10635篇 |
2001年 | 17463篇 |
2000年 | 17458篇 |
1999年 | 13961篇 |
1998年 | 5079篇 |
1997年 | 5334篇 |
1996年 | 4959篇 |
1995年 | 4655篇 |
1994年 | 4542篇 |
1993年 | 4590篇 |
1992年 | 11651篇 |
1991年 | 11566篇 |
1990年 | 11351篇 |
1989年 | 10966篇 |
1988年 | 10535篇 |
1987年 | 10114篇 |
1986年 | 9380篇 |
1985年 | 9256篇 |
1984年 | 7790篇 |
1983年 | 6739篇 |
1982年 | 5184篇 |
1981年 | 4656篇 |
1980年 | 4493篇 |
1979年 | 7439篇 |
1978年 | 5884篇 |
1977年 | 5422篇 |
1976年 | 5217篇 |
1975年 | 5612篇 |
1974年 | 6311篇 |
1973年 | 6187篇 |
1972年 | 5776篇 |
1971年 | 5239篇 |
1970年 | 4649篇 |
1969年 | 4590篇 |
1968年 | 4428篇 |
排序方式: 共有10000条查询结果,搜索用时 20 毫秒
891.
Aaron Mendez-Bermudez Alberto Hidalgo-Bravo Victoria E. Cotton Athanasia Gravani Jennie N. Jeyapalan Nicola J. Royle 《Nucleic acids research》2012,40(21):10809-10820
Approximately 10% of all cancers, but a higher proportion of sarcomas, use the recombination-based alternative lengthening of telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN, play important roles in homologous recombination repair and they have been implicated in telomeric recombination activity, but their precise roles in ALT are unclear. Using analysis of sequence variation present in human telomeres, we found that a WRN– ALT+ cell line lacks the class of complex telomere mutations attributed to inter-telomeric recombination in other ALT+ cell lines. This suggests that WRN facilitates inter-telomeric recombination when there are sequence differences between the donor and recipient molecules or that sister-telomere interactions are suppressed in the presence of WRN and this promotes inter-telomeric recombination. Depleting BLM in the WRN– ALT+ cell line increased the mutation frequency at telomeres and at the MS32 minisatellite, which is a marker of ALT. The absence of complex telomere mutations persisted in BLM-depleted clones, and there was a clear increase in sequence homogenization across the telomere and MS32 repeat arrays. These data indicate that BLM suppresses unequal sister chromatid interactions that result in excessive homogenization at MS32 and at telomeres in ALT+ cells. 相似文献
892.
L.E. Palma-Cano H.A. Piñon-Castillo S.H. Tarango-Rivero A. Carbon J. Salas-Leiva L.N. Muñoz-Castellanos C. Cravo-Laureau R. Duran E. Orrantia-Borunda 《Letters in applied microbiology》2021,72(5):556-569
We described the bacterial diversity of walnut grove soils under organic and conventional farming. The bacterial communities of rhizospheric and nonrhizospheric soils of pecan tree (Carya illinoensis K. Koch) were compared considering two phenological stages (sprouting and ripening). Sixteen operational taxonomic units (OTUs) were identified significantly more abundant according to the plant development, only one according to the farming condition, and none according to the soil origin. The OTUs specificaly abundant according to plant development included Actinobateria (2) and Betaproteobacteria (1) related OTUs more abundant at the sprouting stage, while at the fruit ripening (FR) stage the more abundant OTUs were related to Actinobacteria (6), Alphaproteobacteria (6), and unclassified Bacteria (1). The Gaiellaceae OTU18 (Actinobacteria) was more abundant under conventional farming. Thus, our study revealed that the plant development stage was the main factor shaping the bacterial community structure, while less influence was noticed for the farming condition. The bacterial communities exhibited specific metabolic capacities, a large range of carbon sources being used at the FR stage. The identified OTUs specifically more abundant represent indicators providing useful information on soil condition, potential tools for the management of soil bacterial communities. 相似文献
893.
894.
895.
D Mitchell H P Laburn K E Cooper R F Hellon W I Cranston Y Townsend 《The Yale journal of biology and medicine》1986,59(2):159-168
We have reviewed the evidence in favor of a prostaglandin mediator of the thermal responses in fever and found that PGE injected into the hypothalamus does not always cause fever, that cerebrospinal fluid concentrations of PGE are not reliable reflections of hypothalamic events, and that antipyretic drugs may act in ways other than inhibiting PGE synthesis. Fever is not blocked by prostaglandin antagonists, nor by ablation of PGE-sensitive areas of the brain. There is poor correlation between the effects of pyrogens and of PGE on cerebral neurons. There is evidence that at least one prostanoid other than prostaglandin is a mediator of fever, but the prostanoid has not been identified yet. We conclude that PGE may contribute to the neural responses in fever but is not essential. 相似文献
896.
Eliane S. Meier Thomas C. Edwards Jr Felix Kienast Matthias Dobbertin Niklaus E. Zimmermann 《Journal of Biogeography》2011,38(2):371-382
Aim During recent and future climate change, shifts in large‐scale species ranges are expected due to the hypothesized major role of climatic factors in regulating species distributions. The stress‐gradient hypothesis suggests that biotic interactions may act as major constraints on species distributions under more favourable growing conditions, while climatic constraints may dominate under unfavourable conditions. We tested this hypothesis for one focal tree species having three major competitors using broad‐scale environmental data. We evaluated the variation of species co‐occurrence patterns in climate space and estimated the influence of these patterns on the distribution of the focal species for current and projected future climates. Location Europe. Methods We used ICP Forest Level 1 data as well as climatic, topographic and edaphic variables. First, correlations between the relative abundance of European beech (Fagus sylvatica) and three major competitor species (Picea abies, Pinus sylvestris and Quercus robur) were analysed in environmental space, and then projected to geographic space. Second, a sensitivity analysis was performed using generalized additive models (GAM) to evaluate where and how much the predicted F. sylvatica distribution varied under current and future climates if potential competitor species were included or excluded. We evaluated if these areas coincide with current species co‐occurrence patterns. Results Correlation analyses supported the stress‐gradient hypothesis: towards favourable growing conditions of F. sylvatica, its abundance was strongly linked to the abundance of its competitors, while this link weakened towards unfavourable growing conditions, with stronger correlations in the south and at low elevations than in the north and at high elevations. The sensitivity analysis showed a potential spatial segregation of species with changing climate and a pronounced shift of zones where co‐occurrence patterns may play a major role. Main conclusions Our results demonstrate the importance of species co‐occurrence patterns for calibrating improved species distribution models for use in projections of climate effects. The correlation approach is able to localize European areas where inclusion of biotic predictors is effective. The climate‐induced spatial segregation of the major tree species could have ecological and economic consequences. 相似文献
897.
Molecular mechanisms of ceramide-mediated CD95 clustering. 总被引:2,自引:0,他引:2
H Grassmé H Schwarz E Gulbins 《Biochemical and biophysical research communications》2001,284(4):1016-1030
Receptor clustering has been suggested as a crucial mechanism to initiate receptor signaling. Here we show that ceramide in sphingolipid-rich membrane rafts mediates clustering of CD95. Neutralization of surface ceramide or inhibition of its endogenous generation prevented CD95 clustering. Furthermore, application of ceramide at the cell surface triggered clustering of active but not inactive CD95. Apoptosis was inhibited by neutralization of surface ceramide or inhibition of ceramide release in vitro and in vivo. Thus, we conclude that surface ceramide mediates CD95 clustering, which is required for initiation of apoptosis, at least in some cell types. 相似文献
898.
S. E. Franklin L. Young D. Watson A. Cigan T. Meyer L. A. Bulla Jr. 《Molecular genetics and genomics : MGG》1997,256(5):517-524
Various subspecies of the gram-positive bacterium Bacillus thuringiensis are known to produce a wide array of insecticidal crystal proteins (ICPs) upon sporulation. These ICPs act primarily on the brush border of midgut epithelial cells of susceptible larvae. Recently, a protein of 210?kDa, isolated from the midgut of Manduca sexta, has been demonstrated to bind the Cry1Ab toxin produced by B. thuringiensis subsp. berliner and is therefore postulated to be involved in mediating the toxicity of Cry1Ab. The cDNA encoding the 210?kDa protein, termed BT-R1 (Bacillus thuringiensis receptor-1), was recently cloned, and shows limited homology to the cadherin superfamily of proteins. Quite naturally, there is a great deal of interest in the characterization of BT-R 1 , the gene encoding the 210?kDa Cry1Ab binding protein. The studies presented here involve the use of various restriction fragments prepared from the cDNA encoding BT-R1 as probes of Southern blots bearing M. sexta genomic DNA cleaved with a variety of restriction endonucleases. These Southern blot data reveal that there are two discrete regions within the M. sexta genome which encode sequences homologous to BT-R1. On the basis of the signal intensities seen on Southern blots, it appears that only one of these genes encodes BT-R1, whereas the other is a closely related homologue. 相似文献
899.
Cellular response to oxidative stress at sulfhydryl group receptor sites on the erythrocyte membrane 总被引:6,自引:0,他引:6
J Reglinski S Hoey W E Smith R D Sturrock 《The Journal of biological chemistry》1988,263(25):12360-12366
Ellman's reagent was used to induce an oxidative stimulus on the exofacial membrane sulfhydryl groups of the human erythrocyte. Thiol-disulfide exchange occurring extracellularly was monitored using resonance Raman spectroscopy, and intracellular changes were observed by 1H spin echo nuclear magnetic resonance spectroscopy of the intact cell. The stimulus caused oxidation and depletion of the glutathione pool, which was followed at higher concentrations of Ellman's reagent by a depletion of intracellular ergothioneine levels. Larger changes are induced intracellularly than would be expected from the stoichiometry of the reaction at the exofacial surface. A mechanism is proposed which links exofacial sulfhydryl receptor sites via the transport proteins to spectrin and glutathione. The consequences for the cellular redox balance of an extracellular stimulus of this type are discussed. 相似文献
900.
Stimulation of 32Pi transport into human erythrocyte ghosts and reconstituted vesicles by Mg2+ and hemoglobin 总被引:1,自引:0,他引:1
Human erythrocyte ghosts catalyze a low rate of 32Pi uptake. A severalfold stimulation of 32Pi uptake was observed after exposure of the membranes to an erythrocyte lysate or to hemoglobin in the presence of Mg2+. Ghosts prepared from erythrocytes that had been exposed to 10 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid showed a marked reduction in 32Pi uptake. Reconstitution of membranes with added phospholipids by freezing and thawing, by octylglucoside dilution or by cholate dialysis, yielded vesicles that catalyzed 32Pi uptake. When membranes were incubated with hemoglobin and Mg2+ prior to reconstitution, the rate of uptake was increased severalfold. The inhibition of hemoglobin and Mg2+-dependent uptake of 32Pi by chloride suggests that the transport in the reconstituted vesicles is catalyzed by the classical inorganic anion transporter. 相似文献