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排序方式: 共有316条查询结果,搜索用时 312 毫秒
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Burton PR Palmer LJ Jacobs K Keen KJ Olson JM Elston RC 《American journal of human genetics》2000,67(6):1505-1514
It is commonly assumed that the parameter estimates of a statistical genetics model that has been adjusted for ascertainment will estimate parameters in the general population from which the ascertained subpopulation was originally drawn. We show that this is true only in certain restricted circumstances. More generally, ascertainment-adjusted parameter estimates reflect parameters in the ascertained subpopulation. In many situations, this shift in perspective is immaterial: the parameters of interest are the same in the ascertained sample and in the population from which it was drawn, and it is therefore irrelevant to which population inferences are presumed to apply. In other circumstances, however, this is not so. This has important implications, particularly for studies investigating the etiology of complex diseases. 相似文献
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The performance of some weakly parametric linkage tests in common use was compared on 200 replicates of oligogenic inheritance from Genetic Analysis Workshop 10. Each random sample for the quantitative trait was dichotomized at different thresholds and also selected through 2 affected sibs, generating 8 combinations of sample and variable. The variance component program SOLAR performed best with a continuous trait, even in selected samples, when the population mean was used. The sib-pair program SIBPAL2 was best in most other cases when the phenotype product, population mean, and empirical estimates of pair correlations were used. The BETA program that introduced phenotype products was slightly more powerful than maximum likelihood scores under the null hypothesis and approached but did not exceed SIBPAL2 under its optimal conditions. Type I errors generally exceeded expectations from a chi(2) test, but were conservative with respect to bounds on lods. All methods can be improved by use of the population mean, empirical correlations, logistic representation for affection status, and correct lods for samples that favour the null hypothesis. It remains uncertain whether all information can be extracted by weakly parametric methods and whether correction for ascertainment bias demands a strongly parametric model. Performance on a standard set of simulated data is indispensable for recognising optimal methods. 相似文献
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We study a two-stage analysis of genetic association for case-control studies. In the first stage, we compare Hardy-Weinberg disequilibrium coefficients between cases and controls and, in the second stage, we apply the Cochran- Armitage trend test. The two analyses are statistically independent when Hardy-Weinberg equilibrium holds in the population, so all the samples are used in both stages. The significance level in the first stage is adaptively determined based on its conditional power. Given the level in the first stage, the level for the second stage analysis is determined with the overall Type I error being asymptotically controlled. For finite sample sizes, a parametric bootstrap method is used to control the overall Type I error rate. This two-stage analysis is often more powerful than the Cochran-Armitage trend test alone for a large association study. The new approach is applied to SNPs from a real study. 相似文献
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A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence 总被引:3,自引:0,他引:3
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Lou XY Chen GB Yan L Ma JZ Zhu J Elston RC Li MD 《American journal of human genetics》2007,80(6):1125-1137
The determination of gene-by-gene and gene-by-environment interactions has long been one of the greatest challenges in genetics. The traditional methods are typically inadequate because of the problem referred to as the "curse of dimensionality." Recent combinatorial approaches, such as the multifactor dimensionality reduction (MDR) method, the combinatorial partitioning method, and the restricted partition method, have a straightforward correspondence to the concept of the phenotypic landscape that unifies biological, statistical genetics, and evolutionary theories. However, the existing approaches have several limitations, such as not allowing for covariates, that restrict their practical use. In this study, we report a generalized MDR (GMDR) method that permits adjustment for discrete and quantitative covariates and is applicable to both dichotomous and continuous phenotypes in various population-based study designs. Computer simulations indicated that the GMDR method has superior performance in its ability to identify epistatic loci, compared with current methods in the literature. We applied our proposed method to a genetics study of four genes that were reported to be associated with nicotine dependence and found significant joint action between CHRNB4 and NTRK2. Moreover, our example illustrates that the newly proposed GMDR approach can increase prediction ability, suggesting that its use is justified in practice. In summary, GMDR serves the purpose of identifying contributors to population variation better than do the other existing methods. 相似文献
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