全文获取类型
收费全文 | 6019篇 |
免费 | 585篇 |
国内免费 | 3篇 |
专业分类
6607篇 |
出版年
2024年 | 8篇 |
2023年 | 44篇 |
2022年 | 117篇 |
2021年 | 205篇 |
2020年 | 114篇 |
2019年 | 125篇 |
2018年 | 163篇 |
2017年 | 118篇 |
2016年 | 211篇 |
2015年 | 393篇 |
2014年 | 407篇 |
2013年 | 476篇 |
2012年 | 618篇 |
2011年 | 548篇 |
2010年 | 314篇 |
2009年 | 275篇 |
2008年 | 398篇 |
2007年 | 376篇 |
2006年 | 353篇 |
2005年 | 292篇 |
2004年 | 271篇 |
2003年 | 231篇 |
2002年 | 186篇 |
2001年 | 40篇 |
2000年 | 20篇 |
1999年 | 25篇 |
1998年 | 53篇 |
1997年 | 29篇 |
1996年 | 19篇 |
1995年 | 17篇 |
1994年 | 21篇 |
1993年 | 14篇 |
1992年 | 17篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 8篇 |
1979年 | 5篇 |
1976年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有6607条查询结果,搜索用时 15 毫秒
41.
Common bacterial responses in six ecosystems exposed to 10 years of elevated atmospheric carbon dioxide 总被引:1,自引:0,他引:1
Dunbar J Eichorst SA Gallegos-Graves LV Silva S Xie G Hengartner NW Evans RD Hungate BA Jackson RB Megonigal JP Schadt CW Vilgalys R Zak DR Kuske CR 《Environmental microbiology》2012,14(5):1145-1158
Six terrestrial ecosystems in the USA were exposed to elevated atmospheric CO(2) in single or multifactorial experiments for more than a decade to assess potential impacts. We retrospectively assessed soil bacterial community responses in all six-field experiments and found ecosystem-specific and common patterns of soil bacterial community response to elevated CO(2) . Soil bacterial composition differed greatly across the six ecosystems. No common effect of elevated atmospheric CO(2) on bacterial biomass, richness and community composition across all of the ecosystems was identified, although significant responses were detected in individual ecosystems. The most striking common trend across the sites was a decrease of up to 3.5-fold in the relative abundance of Acidobacteria Group 1 bacteria in soils exposed to elevated CO(2) or other climate factors. The Acidobacteria Group 1 response observed in exploratory 16S rRNA gene clone library surveys was validated in one ecosystem by 100-fold deeper sequencing and semi-quantitative PCR assays. Collectively, the 16S rRNA gene sequencing approach revealed influences of elevated CO(2) on multiple ecosystems. Although few common trends across the ecosystems were detected in the small surveys, the trends may be harbingers of more substantive changes in less abundant, more sensitive taxa that can only be detected by deeper surveys. Representative bacterial 16S rRNA gene clone sequences were deposited in GenBank with Accession No. JQ366086–JQ387568. 相似文献
42.
Genevieve H. L. Roberts Stephanie A. Santorico Richard A. Spritz 《Pigment cell & melanoma research》2020,33(1):8-15
Vitiligo is an autoimmune disease in which destruction of skin melanocytes results in patches of white skin and hair. Genome‐wide linkage studies and genome‐wide association studies in European ancestry cases identified over 50 vitiligo susceptibility loci, defining a model of melanocyte‐directed autoimmunity. Vitiligo heritability is exceedingly high, ~2/3 coming from common and ~1/3 from rare genomic variants; ~20% of vitiligo risk is environmental. Vitiligo genetic risk is polygenic, with greater additive risk in multiplex vitiligo families than simplex cases. Vitiligo age‐of‐onset is bimodal, also involving a major genetic component; a MHC enhancer haplotype confers extreme risk for vitiligo (OR 8.1) and early disease onset, increasing expression of HLA‐DQB1 mRNA and HLA‐DQ protein and thus perhaps facilitating presentation of triggering antigens. Vitiligo triggering also involves a major environmental component; dramatic delay in vitiligo age‐of‐onset, especially from 1973 to 2004, suggests that exposure or response to a key vitiligo environmental trigger diminished during this period. Together, these findings provide deep understanding of vitiligo pathogenesis and genetic architecture, suggesting that vitiligo represents a tractable model for investigating complex disease genetic architecture and predictive aspects of personalized medicine. 相似文献
43.
Inken Kirschbaum Joana Straub Stephanie Gest Martin Holtmann Tanja Legenbauer 《Chronobiology international》2018,35(1):101-110
Chronotherapeutics are well established for the treatment of depression and associated sleeping problems in adults. However, effects are still understudied in adolescents. Two pilot studies highlighted the crucial role of sleep when it comes to the treatment of depression, by means of chronotherapeutics, in adolescents. The aim of the present study was to investigate the role of adjunctive wake therapy (WT) in addition to bright light therapy (BLT) with respect to sleep behaviors. In the present study, 62 depressed inpatients (aged 13–18 years; diagnosed with Beck Depression Inventory Revision) were randomly assigned to two groups: BLT only (BLT-group) and a combination of BLT and WT (COMB-group). After one night of WT adolescents in the COMB-group revealed longer sleep durations, time in bed, advanced sleep onset, less wakes during night and an improved sleep efficiency. However, one night of WT plus BLT had no additional effect on sleep parameters compared with BLT-group in the long run. Therefore, future studies should assess whether more nights of WT might lead to more sustainable effects. 相似文献
44.
Predictions of stream nutrient and sediment yield changes following restoration of forested riparian buffers 总被引:6,自引:1,他引:6
Stephanie M. Parkyn Robert J. Davies-Colley A. Bryce Cooper Morag J. Stroud 《Ecological Engineering》2005,24(5):551-558
Riparian tree planting is widely recognised as a means to improve water quality and stream habitat. However, shading of riparian pasture grasses can lead to channel widening, and riparian shade may limit the growth of macrophytes and algae that assimilate dissolved nutrients from the water column. We investigated concerns that riparian management could lead to increased yields of nutrients and sediments through a conceptual modelling exercise. A simple model of the trade-off between interception of nutrients in runoff by forest buffers versus reduction of in-stream uptake due to shade, predicted that a buffer strip alongside a small headwater stream would reduce nutrient export, while a buffer strip instigated as an isolated patch alongside a larger stream (c. >2.5 km2 upstream catchment size) would increase nutrient export, as the relative amount of nutrients trapped by the buffer decreases as the nutrient load present in the stream water increases. However, in these larger streams with width exceeding approximately 6 m, sufficient light may reach the streambed for plant and algal growth, which in turn would promote instream nutrient processing. At the peak of streambank erosion after planting, predicted total sediment yield (hillslope plus bank sources) was appreciably higher than the hillslope pasture yield, but sediment yield stabilised c. 35–40 years after planting. When planting was extended over 40 years in the model, the sediment yield never exceeded that in pasture before planting. This conceptual modelling exercise shows that riparian tree planting programmes should commence in the headwaters and progress downstream to avoid nutrient yield increases. Significant sediment yield from bank stored sediment of small streams can be expected until the channel reaches the more stable, original forested width, but progressive planting may decrease the peak loads of sediment. 相似文献
45.
Immune suppression remains a consistent obstacle to successful anti-tumor immune responses. As tumors develop, they create
a microenvironment that not only supports tumor growth and metastasis but also reduces potential adaptive immunity to tumor
antigens. Among the many components of this tumor microenvironment is a population of dendritic cells which exert profound
immune suppressive effects on T cells. In this review, we discuss our recent findings related to these tumor-associated dendritic
cells and how targeting them may serve to generate more durable anti-tumor immune responses. 相似文献
46.
Seav‐Ly Tran Lucile Billoud Steven B. Lewis Alan D. Phillips Stephanie Schüller 《Cellular microbiology》2014,16(8):1255-1266
Haemolytic uraemic syndrome caused by Shiga toxin‐producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx‐related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx‐related events and enhance Stx absorption during STEC infection. 相似文献
47.
Bulwin GC Wälter S Schlawinsky M Heinemann T Schulze A Höhne W Krause G Kalka-Moll W Fraser P Volk HD Löhler J Milford EL Utku N 《PloS one》2008,3(2):e1576
Classically, HLA-DR expressed on antigen presenting cells (APC) initiates lymphocyte activation via presentation of peptides to TCR bearing CD4+ T-Cells. Here we demonstrate that HLA-DR alpha 2 domain (sHLA-DRalpha2) also induces negative signals by engaging TIRC7 on lymphocytes. This interaction inhibits proliferation and induces apoptosis in CD4+ and CD8+ T-cells via activation of the intrinsic pathway. Proliferation inhibition is associated with SHP-1 recruitment by TIRC7, decreased phosphorylation of STAT4, TCR-zeta chain & ZAP70, and inhibition of IFN-gamma and FasL expression. HLA-DRalpha2 and TIRC7 co-localize at the APC-T cell interaction site. Triggering HLA-DR - TIRC7 pathway demonstrates that sHLA-DRalpha2 treatment inhibits proinflammatory-inflammatory cytokine expression in APC & T cells after lipopolysaccaride (LPS) stimulation in vitro and induces apoptosis in vivo. These results suggest a novel antiproliferative role for HLA-DR mediated via TIRC7, revise the notion of an exclusive stimulatory interaction of HLA-DR with CD4+ T cells and highlights a novel physiologically relevant regulatory pathway. 相似文献
48.
The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation 总被引:5,自引:0,他引:5
Wang G Chuang L Zhang X Colton S Dombkowski A Reiners J Diakiw A Xu XS 《Nucleic acids research》2004,32(7):2231-2240
XPC is an important DNA damage recognition protein involved in DNA nucleotide excision repair. We have studied the role of the XPC protein in cisplatin treatment-mediated cell cycle regulation. Through the comparison of microarray data obtained from human normal fibroblasts and two individual XPC-defective cell lines, 486 genes were identified as XPC-responsive genes in the cisplatin treatment (with a minimal 1.5-fold change) and 297 of these genes were further mapped to biological pathways and gene ontologies. The cell cycle and cell proliferation-related genes were the most affected genes by the XPC defect in the cisplatin treatment. Many other cellular function genes were also affected by the XPC defect in the treatment. Western blot hybridization results revealed that the XPC defect reduced the p53 responses to the cisplatin treatment. The ability to activate caspase-3 was also attenuated in the XPC cells with the treatment. These results suggest that the XPC protein plays a critical role in initiating the cisplatin DNA damaging treatment-mediated signal transduction process, resulting in activation of the p53 pathway and cell cycle arrest that allow DNA repair and apoptosis to take place. These results reveal an important role of the XPC protein in the cancer prevention. 相似文献
49.
50.
Garcia BA Hake SB Diaz RL Kauer M Morris SA Recht J Shabanowitz J Mishra N Strahl BD Allis CD Hunt DF 《The Journal of biological chemistry》2007,282(10):7641-7655
Post-translational modifications (PTMs) of histones play an important role in many cellular processes, notably gene regulation. Using a combination of mass spectrometric and immunobiochemical approaches, we show that the PTM profile of histone H3 differs significantly among the various model organisms examined. Unicellular eukaryotes, such as Saccharomyces cerevisiae (yeast) and Tetrahymena thermophila (Tet), for example, contain more activation than silencing marks as compared with mammalian cells (mouse and human), which are generally enriched in PTMs more often associated with gene silencing. Close examination reveals that many of the better-known modified lysines (Lys) can be either methylated or acetylated and that the overall modification patterns become more complex from unicellular eukaryotes to mammals. Additionally, novel species-specific H3 PTMs from wild-type asynchronously grown cells are also detected by mass spectrometry. Our results suggest that some PTMs are more conserved than previously thought, including H3K9me1 and H4K20me2 in yeast and H3K27me1, -me2, and -me3 in Tet. On histone H4, methylation at Lys-20 showed a similar pattern as H3 methylation at Lys-9, with mammals containing more methylation than the unicellular organisms. Additionally, modification profiles of H4 acetylation were very similar among the organisms examined. 相似文献