全文获取类型
收费全文 | 2321篇 |
免费 | 123篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 26篇 |
2021年 | 39篇 |
2020年 | 26篇 |
2019年 | 48篇 |
2018年 | 50篇 |
2017年 | 34篇 |
2016年 | 59篇 |
2015年 | 108篇 |
2014年 | 110篇 |
2013年 | 194篇 |
2012年 | 157篇 |
2011年 | 166篇 |
2010年 | 108篇 |
2009年 | 109篇 |
2008年 | 139篇 |
2007年 | 153篇 |
2006年 | 130篇 |
2005年 | 103篇 |
2004年 | 103篇 |
2003年 | 101篇 |
2002年 | 92篇 |
2001年 | 21篇 |
2000年 | 20篇 |
1999年 | 28篇 |
1998年 | 21篇 |
1997年 | 25篇 |
1996年 | 21篇 |
1995年 | 19篇 |
1994年 | 8篇 |
1993年 | 24篇 |
1992年 | 11篇 |
1991年 | 16篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 9篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1972年 | 4篇 |
1959年 | 3篇 |
排序方式: 共有2445条查询结果,搜索用时 31 毫秒
161.
Elections, specially in countries such as Brazil, with an electorate of the order of 100 million people, yield large-scale data-sets embodying valuable information on the dynamics through which individuals influence each other and make choices. In this work we perform an extensive analysis of data sets available for Brazilian proportional elections of legislators and city councilors throughout the period 1970–2014, which embraces two distinct political regimes: a military regime followed by a democratic one. We perform a comparative analysis of elections for legislative positions, in different states and years, through the distribution p(v) of the number of candidates receiving v votes. We show the impact of the different political regimes on the vote distributions. Although p(v) has a common shape, with a scaling behavior, quantitative details change over time and from one electorate to another. In order to interpret the observed features, we propose a multi-species model consisting in a system of nonlinear differential equations, with values of the parameters that reflect the heterogeneity of candidates. In its simplest setting, the model can not explain the cutoff, formed by the most voted candidates, whose success is determined mainly by their peculiar, intrinsic characteristics, such as previous publicity. However, the modeling allows to interpret the scaling of p(v), yielding a predictor of the degree of feedback in the interactions of the electorate. Knowledge of the feedback is relevant beyond the context of elections, since a similar interactivity may occur for other social contagion processes in the same population. 相似文献
162.
Huifen Wang David R. Jacobs Jr Angelo L. Gaffo Myron D. Gross David C. Goff Jr J. Jeffrey Carr 《PloS one》2015,10(9)
Objective
There is controversy about whether serum urate (sUA) predicts future cardiovascular disease (CVD) independently of classical risk factors, and the age at which any prediction starts. We studied the sUA-CVD association among generally healthy adults.Methods
CARDIA recruited 5115 black and white individuals aged 18–30 years in 1985–1986 (year-0). Fatal and nonfatal CVD events by year 27 (n = 164) were ascertained during annual contacts and classified using medical records. The association with sUA (year-0, 10, 15 and 20) was modeled using Cox proportional hazards regression, pooling over gender-specific quartiles.Results
Mean sUA concentration was higher in men than women, but increased over time in both genders. Those with elevated sUA had worse metabolic profiles that substantially deteriorated over time. Adjusting for demographic and lifestyle factors (the minimal model), baseline sUA concentration was positively associated with incident CVD (hazard ratio (HR) per mg/dL = 1.21; 95% confidence interval: 1.05, 1.39; P = 0.005). This positive association attenuated to nonsignificance in the full model accounting simultaneously for classical CVD risk factors (HR = 1.09; 0.94, 1.27; P = 0.24). Both the minimal and full models appeared to show stronger associations (than year-0 sUA) between year-10 sUA and incident CVD (HR = 1.27 and 1.12, respectively), but sUA was not statistically significant in the full model. Despite fewer events, year-15 sUA showed a significant sUA-CVD association pattern, with minimal model association magnitude comparable to year-10, and remained significant in the full model (HR = 1.19; 1.02, 1.40; P = 0.03). Hyperuricemia at year-15 strongly predicted CVD risk (HR = 2.11; 1.34, 3.33; P = 0.001), with some attenuation in the full model (HR = 1.68; P = 0.04).Conclusions
sUA may be an early biomarker for CVD in adults entering middle age. The prediction of CVD by sUA appeared to strengthen with aging. The potential complex relation of sUA with deterioration of a cluster of metabolic abnormalities warrants future exploration. 相似文献163.
Ashini Bolia Brian W. Woodrum Angelo Cereda Melissa A. Ruben Xu Wang S. Banu Ozkan Giovanna Ghirlanda 《Biophysical journal》2014
Cyanovirin-N (CVN), a cyanobacterial lectin, exemplifies a class of antiviral agents that inhibit HIV by binding to the highly glycosylated envelope protein gp120. Here, we investigate the energetics of glycan recognition using a computationally inexpensive flexible docking approach, backbone perturbation docking (BP-Dock). We benchmarked our method using two mutants of CVN: P51G-m4-CVN, which binds dimannose with high affinity through domain B, and CVN(mutDB), in which binding to domain B has been abolished through mutation of five polar residues to small nonpolar side chains. We investigated the energetic contribution of these polar residues along with the additional position 53 by docking dimannose to single-point CVN mutant models. Analysis of the docking simulations indicated that the E41A/G and T57A mutations led to a significant decrease in binding energy scores due to rearrangements of the hydrogen-bond network that reverberated throughout the binding cavity. N42A decreased the binding score to a level comparable to that of CVN(mutDB) by affecting the integrity of the local protein structure. In contrast, N53S resulted in a high binding energy score, similar to P51G-m4-CVN. Experimental characterization of the five mutants by NMR spectroscopy confirmed the binding affinity pattern predicted by BP-Dock. Despite their mostly conserved fold and stability, E41A, E41G, and T57A displayed dissociation constants in the millimolar range. N53S showed a binding constant in the low micromolar range, similar to that observed for P51G-m4-CVN. No binding was observed for N42A. Our results show that BP-Dock is a useful tool for rapidly screening the relative binding affinity pattern of in silico-designed mutants compared with wild-type, supporting its use to design novel mutants with enhanced binding properties. 相似文献
164.
165.
166.
Facchiano Francesco Deloye Florence Doussau Frédéric Innamorati Giulio Ashton Anthony C. Dolly J. Oliver Beninati Simone Facchiano Angelo Luini Alberto Poulain Bernard Benfenati Fabio 《Amino acids》2010,38(1):257-262
The aim of this study was to collect evidences on the role of transglutaminase (TG, E.C.2.3.2.13) in the antineoplastic properties
exerted by nimesulide (NMS), a non-steroidal anti-inflammatory drug, on murine B16-F10 melanoma cells. Treatment of melanoma
cells with nimesulide produces a considerable reduction of cell proliferation, paralleled by a remarkable decrease of the
intracellular concentration of polyamines spermidine and spermine. NMS treatment induces cancer cell differentiation, likely
through the observed enhancement of TG and tyrosinase activities and increase of melanin production, well known markers of
melanocyte differentiation. The overall results highlight the possibility that nimesulide acts as antineoplastic agent likely
through the induction of intracellular TG activity. 相似文献
167.
Haag T Santos AS Sana DA Morato RG Cullen L Crawshaw PG De Angelo C Di Bitetti MS Salzano FM Eizirik E 《Molecular ecology》2010,19(22):4906-4921
Habitat fragmentation may disrupt original patterns of gene flow and lead to drift-induced differentiation among local population units. Top predators such as the jaguar may be particularly susceptible to this effect, given their low population densities, leading to small effective sizes in local fragments. On the other hand, the jaguar's high dispersal capabilities and relatively long generation time might counteract this process, slowing the effect of drift on local populations over the time frame of decades or centuries. In this study, we have addressed this issue by investigating the genetic structure of jaguars in a recently fragmented Atlantic Forest region, aiming to test whether loss of diversity and differentiation among local populations are detectable, and whether they can be attributed to the recent effect of drift. We used 13 microsatellite loci to characterize the genetic diversity present in four remnant populations, and observed marked differentiation among them, with evidence of recent allelic loss in local areas. Although some migrant and admixed individuals were identified, our results indicate that recent large-scale habitat removal and fragmentation among these areas has been sufficiently strong to promote differentiation induced by drift and loss of alleles at each site. Low estimated effective sizes supported the inference that genetic drift could have caused this effect within a short time frame. These results indicate that jaguars' ability to effectively disperse across the human-dominated landscapes that separate the fragments is currently very limited, and that each fragment contains a small, isolated population that is already suffering from the effects of genetic drift. 相似文献
168.
Bruna Vinci Ellen Murphy Elisabetta Iori Maria Cristina Marescotti Angelo Avogaro Arti Ahluwalia Professor 《Biotechnology journal》2010,5(6):618-626
Static cell culture has serious limitations in its ability to represent cellular behaviour within a live organism. In vivo, cells are constantly exposed to the flow of bodily fluids and contact with other cell types. Bioreactors provide the opportunity to study cells in an environment that more closely resembles the in vivo setting because cell cultures can be exposed to dynamic flow in contact with or in proximity to other cell types. In this study we compared the metabolic profile of a dynamic cell culture system to that of a static cell culture in three different cellular phenotypes: adipocytes, endothelial cells and hepatocytes. Albumin, glucose, free fatty acids, glycerol, and lactate were measured over 48 h. We show that all three cell types have increased glucose uptake in the presence of flow; lactate release was also significantly affected. We provide robust evidence that the presence of flow significantly modifies cellular metabolism. While flow provides a more uniform nutrient distribution and increases metabolite turnover, our results indicate that different cell types have specific metabolic responses to flow, suggesting cell-specific flow-regulated activation of metabolite signalling pathways. 相似文献
169.
Alberto Biscontin Silvia Casara Stefano Cagnin Lucia Tombolan Angelo Rosolen Gerolamo Lanfranchi Cristiano De Pittà 《BMC molecular biology》2010,11(1):44
Background
microRNAs (miRNAs) are small single-stranded non-coding RNAs that act as crucial regulators of gene expression. Different methods have been developed for miRNA expression profiling in order to better understand gene regulation in normal and pathological conditions. miRNAs expression values obtained from large scale methodologies such as microarrays still need a validation step with alternative technologies. 相似文献170.
Proteomics and transcriptomics investigation on longissimus muscles in Large White and Casertana pig breeds 总被引:1,自引:0,他引:1
Murgiano L D'Alessandro A Egidi MG Crisà A Prosperini G Timperio AM Valentini A Zolla L 《Journal of proteome research》2010,9(12):6450-6466
Consumer complaints against the blandness of modern lean meat and the frequent reference to the more strongly flavored meat that was available years ago have prompted reconsideration of high fat-depositing typical pig breeds. Casertana and Large White pig breeds are characterized by a different tendency toward fat accumulation as they exhibit opposite genetic and physiological traits with respect to the energy metabolism. These physiological differences were investigated in longissimus lumborum muscles through proteomics (2-DE, MS/MS) and microarray approaches. Data were analyzed for pathway and network analyses, as well as GO term enrichment of biological functions. As a result, Casertana showed a greater amount of proteins involved in glycolitic metabolism and mainly rely on fast-mobilizable energy sources. Large White overexpressed cell cycle and skeletal muscle growth related genes. Metabolic behavior and other implications are discussed. 相似文献