全文获取类型
收费全文 | 8214篇 |
免费 | 657篇 |
国内免费 | 8篇 |
专业分类
8879篇 |
出版年
2024年 | 11篇 |
2023年 | 57篇 |
2022年 | 142篇 |
2021年 | 305篇 |
2020年 | 165篇 |
2019年 | 223篇 |
2018年 | 234篇 |
2017年 | 194篇 |
2016年 | 334篇 |
2015年 | 474篇 |
2014年 | 500篇 |
2013年 | 594篇 |
2012年 | 697篇 |
2011年 | 679篇 |
2010年 | 428篇 |
2009年 | 338篇 |
2008年 | 493篇 |
2007年 | 443篇 |
2006年 | 370篇 |
2005年 | 341篇 |
2004年 | 339篇 |
2003年 | 277篇 |
2002年 | 314篇 |
2001年 | 73篇 |
2000年 | 42篇 |
1999年 | 68篇 |
1998年 | 43篇 |
1997年 | 50篇 |
1996年 | 45篇 |
1995年 | 29篇 |
1994年 | 25篇 |
1993年 | 28篇 |
1992年 | 30篇 |
1991年 | 21篇 |
1990年 | 15篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 22篇 |
1986年 | 16篇 |
1985年 | 20篇 |
1982年 | 19篇 |
1981年 | 21篇 |
1980年 | 16篇 |
1978年 | 13篇 |
1976年 | 10篇 |
1975年 | 12篇 |
1970年 | 10篇 |
1968年 | 15篇 |
1966年 | 11篇 |
1962年 | 9篇 |
排序方式: 共有8879条查询结果,搜索用时 15 毫秒
71.
Edmond M. Linossi Indu R. Chandrashekaran Tatiana B. Kolesnik James M. Murphy Andrew I. Webb Tracy A. Willson Lukasz Kedzierski Alex N. Bullock Jeffrey J. Babon Raymond S. Norton Nicos A. Nicola Sandra E. Nicholson 《PloS one》2013,8(8)
Suppressor of Cytokine Signaling (SOCS)5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF) signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR). Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2) autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling. 相似文献
72.
73.
Melles DC van Leeuwen WB Snijders SV Horst-Kreft D Peeters JK Verbrugh HA van Belkum A 《Journal of microbiological methods》2007,69(2):371-375
We compared multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and amplified fragment length polymorphism (AFLP) for typing of Staphylococcus aureus and show that the methods yield similar results, although with differences in resolving power and reproducibility. Epidemiological conditions should determine which is the optimal typing method to be used. 相似文献
74.
Li SH Sun Z Guo L Han M Wood MF Ghosh N Alex Vitkin I Weisel RD Li RK 《Journal of cellular and molecular medicine》2012,16(10):2429-2439
After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re‐establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full‐length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P < 0.05 versus controls). As a result, infarct scar thickness and diastolic compliance were maintained and infarct expansion was prevented (P < 0.05 versus controls). Over a 9‐week period, rats implanted with BMSCs demonstrated better cardiac function than medium controls; however, rats receiving BMSCs overexpressing elastin showed the greatest functional improvement (P < 0.01). Overexpression of elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell‐based gene therapy provides a new approach to cardiac regeneration. 相似文献
75.
Scerri TS Paracchini S Morris A MacPhie IL Talcott J Stein J Smith SD Pennington BF Olson RK DeFries JC Monaco AP Richardson AJ 《PloS one》2010,5(10):e13712
Background
Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis.Methodology/Principal Findings
Linkage analysis: 264 UK families and 155 US families each containing at least one child diagnosed with dyslexia were genotyped with a dense set of microsatellite markers on chromosome 18. Association analysis: Using a discovery sample of 187 UK families, nearly 3000 SNPs were genotyped across the chromosome 18 dyslexia susceptibility candidate region. Following association analysis, the top ranking SNPs were then genotyped in the remaining samples. The linkage analysis revealed a broad signal that spans approximately 40 Mb from 18p11.2 to 18q12.2. Following the association analysis and subsequent replication attempts, we observed consistent association with the same SNPs in three genes; melanocortin 5 receptor (MC5R), dymeclin (DYM) and neural precursor cell expressed, developmentally down-regulated 4-like (NEDD4L).Conclusions
Along with already published biological evidence, MC5R, DYM and NEDD4L make attractive candidates for dyslexia susceptibility genes. However, further replication and functional studies are still required. 相似文献76.
Merav Gleit Kielmanowicz Alex Inberg Inbar Maayan Lerner Yael Golani Nicholas Brown Catherine Louise Turner Gerald J. R. Hayes Joan M. Ballam 《PLoS pathogens》2015,11(4)
Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. 相似文献
77.
78.
79.
Rogers AD 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2007,362(1488):2191-2214
The Antarctic biota is highly endemic, and the diversity and abundance of taxonomic groups differ from elsewhere in the world. Such characteristics have resulted from evolution in isolation in an increasingly extreme environment over the last 100 Myr. Studies on Antarctic species represent some of the best examples of natural selection at the molecular, structural and physiological levels. Analyses of molecular genetics data are consistent with the diversity and distribution of marine and terrestrial taxa having been strongly influenced by geological and climatic cooling events over the last 70 Myr. Such events have resulted in vicariance driven by continental drift and thermal isolation of the Antarctic, and in pulses of species range contraction into refugia and subsequent expansion and secondary contact of genetically distinct populations or sister species during cycles of glaciation. Limited habitat availability has played a major role in structuring populations of species both in the past and in the present day. For these reasons, despite the apparent simplicity or homogeneity of Antarctic terrestrial and marine environments, populations of species are often geographically structured into genetically distinct lineages. In some cases, genetic studies have revealed that species defined by morphological characters are complexes of cryptic or sibling species. Climate change will cause changes in the distribution of many Antarctic and sub-Antarctic species through affecting population-level processes such as life history and dispersal. 相似文献
80.
The integrin alphaLbeta2 mediates leukocyte adhesion and migration that are required for a functional immune system. It is known that inside-out signaling triggers alphaLbeta2 conformational changes, which affect its ligand-binding affinity. At least three alphaLbeta2 affinity states (low, intermediate, and high) were described. The cytosolic protein talin connects alphaLbeta2 to the actin filament. The talin head domain is also known to activate alphaLbeta2 ligand binding. However, it remains to be determined whether talin promotes an intermediate or high affinity alphaLbeta2. In this study using transfectants and T cells, we showed that talin induced an intermediate affinity alphaLbeta2 that adhered constitutively to its ligand intercellular adhesion molecule (ICAM)-1 but not ICAM-3. Adhesion to ICAM-3 was induced when an additional exogenous activating agent was included. Similar profiles were observed with soluble ICAMs. In addition, the intermediate affinity alphaLbeta2 induced by talin allowed adhesion and migration of T cells on immobilized ICAMs. 相似文献