全文获取类型
收费全文 | 6978篇 |
免费 | 655篇 |
国内免费 | 2篇 |
出版年
2022年 | 49篇 |
2021年 | 152篇 |
2020年 | 87篇 |
2019年 | 107篇 |
2018年 | 113篇 |
2017年 | 106篇 |
2016年 | 200篇 |
2015年 | 333篇 |
2014年 | 334篇 |
2013年 | 394篇 |
2012年 | 531篇 |
2011年 | 555篇 |
2010年 | 344篇 |
2009年 | 276篇 |
2008年 | 450篇 |
2007年 | 464篇 |
2006年 | 358篇 |
2005年 | 400篇 |
2004年 | 372篇 |
2003年 | 335篇 |
2002年 | 293篇 |
2001年 | 75篇 |
2000年 | 86篇 |
1999年 | 96篇 |
1998年 | 98篇 |
1997年 | 50篇 |
1996年 | 44篇 |
1995年 | 51篇 |
1994年 | 34篇 |
1993年 | 51篇 |
1992年 | 36篇 |
1991年 | 45篇 |
1990年 | 45篇 |
1989年 | 31篇 |
1988年 | 33篇 |
1987年 | 35篇 |
1986年 | 44篇 |
1985年 | 37篇 |
1984年 | 37篇 |
1983年 | 37篇 |
1982年 | 32篇 |
1981年 | 34篇 |
1980年 | 19篇 |
1979年 | 30篇 |
1978年 | 30篇 |
1977年 | 23篇 |
1976年 | 22篇 |
1974年 | 27篇 |
1973年 | 25篇 |
1972年 | 19篇 |
排序方式: 共有7635条查询结果,搜索用时 31 毫秒
981.
Background
This study sought to identify whether elevated risk of infectious intestinal disease (IID) exists in contaminated small water supply consumers compared with consumers drinking from small supplies complying with current standards and whether this effect is modified by age.Methodology and Principal Findings
A prospective cohort study of 611 individuals receiving small supplies in England was conducted. Water supplies received sanitary inspection and examination for indicator bacteria and participants maintained a daily record of IID. Regression modeling with generalized estimating equations that included interaction terms between age and indicators of fecal pollution was performed. Crude IID prevalence was 9·3 days with symptoms/1000 person days (95%CI: 8·4, 10·1) and incidence was 3·2 episodes/1000 person days (95%CI, 2·7, 3·7) or 1·2 episodes per person year. Although there was no overall association between IID risk and indicator presence, there was strong interaction between age and indicator presence. In children under ten, relative risk (RR) of IID in those drinking from enterococci contaminated supplies was 4.8 (95%CI: 1.5, 15.3) for incidence and 8.9 (95%CI: 2.8, 27.5) for prevalence. In those aged 10 to 59, IID risk was lower but not statistically significant.Conclusions
Contaminated small water supplies pose a substantial risk of IID to young children who live in homes reliant on these supplies. By contrast older children and adults do not appear to be at increased risk. Health care professionals with responsibility for children living in homes provided by very small water supplies should make parents aware of the risk. 相似文献982.
We have shown that cystic fibrosis transmembrane conductance regulator (CFTR) is involved in ATP release from skeletal muscle at low pH. These experiments investigate the signal transduction mechanism linking pH depression to CFTR activation and ATP release, and evaluate whether CFTR is involved in ATP release from contracting muscle. Lactic acid treatment elevated interstitial ATP of buffer-perfused muscle and extracellular ATP of L6 myocytes: this ATP release was abolished by the non-specific CFTR inhibitor, glibenclamide, or the specific CFTR inhibitor, CFTRinh-172, suggesting that CFTR was involved, and by inhibition of lactic acid entry to cells, indicating that intracellular pH depression was required. Muscle contractions significantly elevated interstitial ATP, but CFTRinh-172 abolished the increase. The cAMP/PKA pathway was involved in the signal transduction pathway for CFTR-regulated ATP release from muscle: forskolin increased CFTR phosphorylation and stimulated ATP release from muscle or myocytes; lactic acid increased intracellular cAMP, pCREB and PKA activity, whereas IBMX enhanced ATP release from myocytes. Inhibition of PKA with KT5720 abolished lactic-acid- or contraction-induced ATP release from muscle. Inhibition of either the Na+/H+-exchanger (NHE) with amiloride or the Na+/Ca2+-exchanger (NCX) with SN6 or KB-R7943 abolished lactic-acid- or contraction-induced release of ATP from muscle, suggesting that these exchange proteins may be involved in the activation of CFTR. Our data suggest that CFTR-regulated release contributes to ATP release from contracting muscle in vivo, and that cAMP and PKA are involved in the activation of CFTR during muscle contractions or acidosis; NHE and NCX may be involved in the signal transduction pathway. 相似文献
983.
984.
Heather Armstrong Annemarie Wolmarans Rebecca Mercier BaoChan Mai Paul LaPointe 《PloS one》2012,7(11)
Hsp90 is a dimeric ATPase responsible for the activation or maturation of a specific set of substrate proteins termed ‘clients’. This molecular chaperone acts in the context of a structurally dynamic and highly regulated cycle involving ATP, co-chaperone proteins and clients. Co-chaperone proteins regulate conformational transitions that may be impaired in mutant forms of Hsp90. We report here that the in vivo impairment of commonly studied Hsp90 variants harbouring the G313S or A587T mutation are exacerbated by the co-chaperone Hch1p. Deletion of HCH1, but not AHA1, mitigates the temperature sensitive phenotype and high sensitivity to Hsp90 inhibitor drugs observed in Saccharomyces cerevisiae that express either of these two Hsp90 variants. Moreover, the deletion of HCH1 results in high resistance to Hsp90 inhibitors in yeast that express wildtype Hsp90. Conversely, the overexpression of Hch1p greatly increases sensitivity to Hsp90 inhibition in yeast expressing wildtype Hsp90. We conclude that despite the similarity between these two co-chaperones, Hch1p and Aha1p regulate Hsp90 function in distinct ways and likely independent of their roles as ATPase stimulators. We further conclude that Hch1p plays a critical role in regulating Hsp90 inhibitor drug sensitivity in yeast. 相似文献
985.
986.
987.
Recent losses of honey bee colonies have led to increased interest in the microbial communities that are associated with these important pollinators. A critical function that bacteria perform for their honey bee hosts, but one that is poorly understood, is the transformation of worker-collected pollen into bee bread, a nutritious food product that can be stored for long periods in colonies. We used 16S rRNA pyrosequencing to comprehensively characterize in genetically diverse and genetically uniform colonies the active bacterial communities that are found on honey bees, in their digestive tracts, and in bee bread. This method provided insights that have not been revealed by past studies into the content and benefits of honey bee-associated microbial communities. Colony microbiotas differed substantially between sampling environments and were dominated by several anaerobic bacterial genera never before associated with honey bees, but renowned for their use by humans to ferment food. Colonies with genetically diverse populations of workers, a result of the highly promiscuous mating behavior of queens, benefited from greater microbial diversity, reduced pathogen loads, and increased abundance of putatively helpful bacteria, particularly species from the potentially probiotic genus Bifidobacterium. Across all colonies, Bifidobacterium activity was negatively correlated with the activity of genera that include pathogenic microbes; this relationship suggests a possible target for understanding whether microbes provide protective benefits to honey bees. Within-colony diversity shapes microbiotas associated with honey bees in ways that may have important repercussions for colony function and health. Our findings illuminate the importance of honey bee-bacteria symbioses and examine their intersection with nutrition, pathogen load, and genetic diversity, factors that are considered key to understanding honey bee decline. 相似文献
988.
Genera within the South American cichlid tribe Geophagini display specialized feeding and reproductive strategies, with some taxa specialized for both substrate-sifting and mouth brooding. Several lineages within the clade also possess an epibranchial lobe (EBL), a unique pharyngeal structure that has been proposed to have a function in feeding and/or mouth brooding. A recently published genus-level phylogeny of Neotropical cichlids was used as the evolutionary framework for investigating the evolution of morphological features presumably correlated with diet and mouth brooding in the tribe Geophagini. We tested for possible associations between the geophagine epibranchial lobe and benthic feeding and mouth brooding. We also addressed whether the EBL may be associated with unique patterns of diversification in certain geophagine clades. Tests of binary character correlations revealed the EBL was significantly associated with mouth brooding. We also tested for a relationship between diet and morphology. We analyzed stomach contents and morphometric variation among 21 species, with data for two additional species obtained from the literature. Principal Components Analysis revealed axes of morphological variation significantly correlated with piscivory and benthivory, and both morphology and diet were significantly associated with phylogeny. These results suggest that the EBL could be an adaptation for either feeding or mouth brooding. The EBL, however, was not associated with species richness or accelerated rates of phyletic diversification. 相似文献
989.
Angiogenesis is tightly regulated through complex crosstalk between pro- and anti-angiogenic signals. High molecular weight kininogen (HK) is an endogenous protein that is proteolytically cleaved in plasma and on endothelial cell surfaces to HKa, an anti-angiogenic protein. Ferritin binds to HKa and blocks its anti-angiogenic activity. Here, we explore mechanisms underlying the cytoprotective effect of ferritin in endothelial cells exposed to HKa. We observe that ferritin promotes adhesion and survival of HKa-treated cells and restores key survival and adhesion signaling pathways mediated by Erk, Akt, FAK and paxillin. We further elucidate structural motifs of both HKa and ferritin that are required for effects on endothelial cells. We identify an histidine-glycine-lysine (HGK) -rich antiproliferative region within domain 5 of HK as the target of ferritin, and demonstrate that both ferritin subunits of the H and L type regulate HKa activity. We further demonstrate that ferritin reduces binding of HKa to endothelial cells and restores the association of uPAR with α5β1 integrin. We propose that ferritin blocks the anti-angiogenic activity of HKa by reducing binding of HKa to UPAR and interfering with anti-adhesive and anti-proliferative signaling of HKa. 相似文献
990.