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排序方式: 共有102条查询结果,搜索用时 31 毫秒
71.
Yue WH Wang HF Sun LD Tang FL Liu ZH Zhang HX Li WQ Zhang YL Zhang Y Ma CC Du B Wang LF Ren YQ Yang YF Hu XF Wang Y Deng W Tan LW Tan YL Chen Q Xu GM Yang GG Zuo XB Yan H Ruan YY Lu TL Han X Ma XH Wang Y Cai LW Jin C Zhang HY Yan J Mi WF Yin XY Ma WB Liu Q Kang L Sun W Pan CY Shuang M Yang FD Wang CY Yang JL Li KQ Ma X Li LJ Yu X Li QZ Huang X Lv LX Li T Zhao GP Huang W Zhang XJ Zhang D 《Nature genetics》2011,43(12):1228-1231
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia. 相似文献
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The terrestrial and lunar cratering rate is often assumed to have been nearly constant over the past 3 Gyr. Different lines of evidence, however, suggest that the impact flux from kilometre-sized bodies increased by at least a factor of two over the long-term average during the past approximately 100 Myr. Here we argue that this apparent surge was triggered by the catastrophic disruption of the parent body of the asteroid Baptistina, which we infer was a approximately 170-km-diameter body (carbonaceous-chondrite-like) that broke up 160(-20)+30Myr ago in the inner main asteroid belt. Fragments produced by the collision were slowly delivered by dynamical processes to orbits where they could strike the terrestrial planets. We find that this asteroid shower is the most likely source (>90 per cent probability) of the Chicxulub impactor that produced the Cretaceous/Tertiary (K/T) mass extinction event 65 Myr ago. 相似文献
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Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors
Neuhaus B Bühren S Böck B Alves F Vogel WF Kiefer F 《Cellular and molecular life sciences : CMLS》2011,68(22):3757-3770
The non-receptor tyrosine kinase Syk is a well-characterized hematopoietic signal transducer, which is also expressed in non-hematopoietic
cells. In epithelial cells, the function of Syk is not wholly known. It interacts with the receptor tyrosine kinase DDR1 and
is frequently lost from metastatic mammary tumors. Here, using genetic tracing, we demonstrate Syk expression in murine mammary
epithelium, myoepithelium and skin epithelium, but not in intestinal or lung epithelia. Investigating possible functions of
Syk, we found a substantial suppression of cell mobility that depended on Syk kinase activity in trans-well migration and
wounding assays. Co-expression of DDR1 resulted in constitutive interaction and strong activation of Syk kinase. Most importantly,
Syk-mediated migration inhibition was blocked in the presence of DDR1, while conversely DDR1 knockdown restored migration
inhibition. Our study identifies Syk as a potent inhibitor of epithelial migration and describes a first functional consequence
of the interaction with the collagen receptor DDR1. 相似文献
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van der Zanden LF van Rooij IA Feitz WF Knight J Donders AR Renkema KY Bongers EM Vermeulen SH Kiemeney LA Veltman JA Arias-Vásquez A Zhang X Markljung E Qiao L Baskin LS Nordenskjöld A Roeleveld N Franke B Knoers NV 《Nature genetics》2011,43(1):48-50
Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10?11 and OR = 2.3, P = 2.9 × 10??, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10?? and OR = 3.8, P = 3.4 × 10??) and Swedish (OR = 2.5, P = 2.6 × 10?? and OR = 2.2, P = 2.7 × 10??) replication samples. Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias. 相似文献
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To persist, species are expected to shift their geographical ranges polewards or to higher elevations as the Earth's climate warms. However, although many species' ranges have shifted in historical times, many others have not, or have shifted only at the high-latitude or high-elevation limits, leading to range expansions rather than contractions. Given these idiosyncratic responses to climate warming, and their varied implications for species' vulnerability to climate change, a critical task is to understand why some species have not shifted their ranges, particularly at the equatorial or low-elevation limits, and whether such resilience will last as warming continues. Here we show that compensatory changes in demographic rates are buffering southern populations of two North American tundra plants against the negative effects of a warming climate, slowing their northward range shifts, but that this buffering is unlikely to continue indefinitely. Southern populations of both species showed lower survival and recruitment but higher growth of individual plants, possibly owing to longer, warmer growing seasons. Because of these and other compensatory changes, the population growth rates of southern populations are not at present lower than those of northern ones. However, continued warming may yet prove detrimental, as most demographic rates that improved in moderately warmer years declined in the warmest years, with the potential to drive future population declines. Our results emphasize the need for long-term, range-wide measurement of all population processes to detect demographic compensation and to identify nonlinear responses that may lead to sudden range shifts as climatic tipping points are exceeded. 相似文献
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