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The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets. 相似文献
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Harry D. Green Alistair Jones Jonathan P. Evans Andrew R. Wood Robin N. Beaumont Jessica Tyrrell Timothy M. Frayling Christopher Smith Michael N. Weedon 《PLoS genetics》2021,17(6)
Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16–1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren’s disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02–1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren’s disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition. 相似文献
425.
It has not been possible to demonstrate significant sero-genetic differences between lowland and highland Sotho populations; the differences which do exist may well be attributable to random genetic drift. The study shows that the Sotho have received an appreciable genetic contribution from the San they have absorbed but their sero-genetic profile remains eminently Negro. A low frequency of the PTC non-taster allele was found (t = 0.142 +/- 0.029) as was the overall frequency for colour blindness (cb = 0.013 +/- 0.009). 相似文献
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Inhibitors of peripheral-type benzodiazepine receptors present in human urine and plasma ultrafiltrates 总被引:4,自引:0,他引:4
Several endogenous substances that inhibit central-type benzodiazepine (BZD) receptor binding have recently been identified. We have found that ultrafiltrates of human uremic plasma, normal plasma, and urine contain competitive inhibitors of peripheral-type benzodiazepine receptors. Using urine as source, we have partially purified a peripheral-type BZD receptor inhibitor(s) by adsorption to and selective elution from small octadecyl-silane (Sep-pak) columns and thin layer chromatography. The inhibitor has a 125-fold greater affinity for peripheral-type than central-type BZD receptors and has been purified 8000-fold from urine. 相似文献
429.
J. Cucherousset J. R. Britton W. R. C. Beaumont M. Nyqvist K. Sievers R. E. Gozlan 《Journal of fish biology》2010,76(4):1039-1045
The efficiency of portable passive integrated transponder (PIT) telemetry at detecting five fish species in a small river was evaluated under different environmental and tracking conditions. Significant differences between species were apparent, with detection efficiency varying between 0·7% (Leuciscus leuciscus) and 43·1% (Salmo trutta). Conditions of reduced flow and tracking in a downstream direction significantly increased detection efficiency for salmonids, while time of day had no significant effect for any species. 相似文献
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