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排序方式: 共有250条查询结果,搜索用时 15 毫秒
91.
The successful implementation of Bayesian shrinkage analysis of high-dimensional regression models, as often encountered in quantitative trait locus (QTL) mapping, is contingent upon the choice of suitable sparsity-inducing priors. In practice, the shape (that is, the rate of tail decay) of such priors is typically preset, with no regard for the range of plausible alternatives and the fact that the most appropriate shape may depend on the data at hand. This study is presumably the first attempt to tackle this oversight through the shape-adaptive shrinkage prior (SASP) approach, with a focus on the mapping of QTLs in experimental crosses. Simulation results showed that the separation between genuine QTL effects and spurious ones can be made clearer using the SASP-based approach as compared with existing competitors. This feature makes our new method a promising approach to QTL mapping, where good separation is the ultimate goal. We also discuss a re-estimation procedure intended to improve the accuracy of the estimated genetic effects of detected QTLs with regard to shrinkage-induced bias, which may be particularly important in large-scale models with collinear predictors. The re-estimation procedure is relevant to any shrinkage method, and is potentially valuable for many scientific disciplines such as bioinformatics and quantitative genetics, where oversaturated models are booming. 相似文献
92.
Sillanpää MJ 《Molecular ecology》2011,20(7):1324-1332
Here we take a look at molecular marker-based heritability estimation suitable for non-model organisms. We address several theoretical issues involved and discuss similarities and differences between our two main approaches: the animal model approach and the shrinkage-estimation based multilocus association approach. Also computational issues and hypothetical example applications for ecologists are considered. 相似文献
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Dopaminergic (DA) neurons in the substantia nigra pars compacta (also known as A9 DA neurons) are the specific cell type that is lost in Parkinson’s disease (PD). There is great interest in deriving A9 DA neurons from human pluripotent stem cells (hPSCs) for regenerative cell replacement therapy for PD. During neural development, A9 DA neurons originate from the floor plate (FP) precursors located at the ventral midline of the central nervous system. Here, we optimized the culture conditions for the stepwise differentiation of hPSCs to A9 DA neurons, which mimics embryonic DA neuron development. In our protocol, we first describe the efficient generation of FP precursor cells from hPSCs using a small molecule method, and then convert the FP cells to A9 DA neurons, which could be maintained in vitro for several months. This efficient, repeatable and controllable protocol works well in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) from normal persons and PD patients, in which one could derive A9 DA neurons to perform in vitro disease modeling and drug screening and in vivo cell transplantation therapy for PD. 相似文献
96.
Mustonen AM Käkelä R Halonen T Kärjä V Vartiainen E Nieminen P 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2012,163(1):152-160
Factors regulating fatty acid (FA) composition of small herbivores are poorly known. Because of the fast response to food deprivation, the tissue FA profiles of voles could be rapidly modified. The selectivity of incorporating dietary FA into tissue total lipids and mobilizing tissue FA was examined in two Microtus vole species either fed or fasted for 12-18 h. The FA composition of the tissues reflected the dietary lipids, but FA were selectively incorporated depending on their structure. The FA profiles of white and brown adipose tissues were different and contained more saturated and monounsaturated FA and less polyunsaturated FA (PUFA) than the diet. The essential PUFA precursors with smaller tissue percentages were likely converted into longer-chain derivatives for structural lipids. The FA composition of the vole tissues was selectively modified by food deprivation. The preferences for retention or loss were tissue-specific and related to the FA structure. Livers displayed steatosis with characteristic accumulation of triacylglycerols, while FA prevalent in membrane phospholipids decreased in proportion. Hepatic FA could be partly derived from lipids hydrolyzed in fat depots. The FA profiles of the vole tissues reflect the dietary lipids and are rapidly and selectively modified by food deprivation. 相似文献
97.
Crispin M. Mutshinda Mikko J. Sillanp?? 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2012,125(7):1575-1587
Introduction
Virtually all existing expectation-maximization (EM) algorithms for quantitative trait locus (QTL) mapping overlook the covariance structure of genetic effects, even though this information can help enhance the robustness of model-based inferences.Results
Here, we propose fast EM and pseudo-EM-based procedures for Bayesian shrinkage analysis of QTLs, designed to accommodate the posterior covariance structure of genetic effects through a block-updating scheme. That is, updating all genetic effects simultaneously through many cycles of iterations.Conclusion
Simulation results based on computer-generated and real-world marker data demonstrated the ability of our method to swiftly produce sensible results regarding the phenotype-to-genotype association. Our new method provides a robust and remarkably fast alternative to full Bayesian estimation in high-dimensional models where the computational burden associated with Markov chain Monte Carlo simulation is often unwieldy. The R code used to fit the model to the data is provided in the online supplementary material. 相似文献98.
Tammenkoski M Koivula K Cusanelli E Zollo M Steegborn C Baykov AA Lahti R 《Biochemistry》2008,47(36):9707-9713
The DHH superfamily human protein h-prune, a binding partner of the metastasis suppressor nm23-H1, is frequently overexpressed in metastatic cancers. From an evolutionary perspective, h-prune is very close to eukaryotic exopolyphosphatases. Here, we show for the first time that h-prune efficiently hydrolyzes short-chain polyphosphates (k cat of 3-40 s (-1)), including inorganic tripoly- and tetrapolyphosphates and nucleoside 5'-tetraphosphates. Long-chain inorganic polyphosphates (>or=25 phosphate residues) are converted more slowly, whereas pyrophosphate and nucleoside triphosphates are not hydrolyzed. The reaction requires a divalent metal cofactor, such as Mg (2+), Co (2+), or Mn (2+), which activates both the enzyme and substrate. Notably, the exopolyphosphatase activity of h-prune is suppressed by nm23-H1, long-chain polyphosphates and pyrophosphate, which may be potential physiological regulators. Nucleoside triphosphates, diadenosine hexaphosphate, cAMP, and dipyridamole (inhibitor of phosphodiesterase) do not affect this activity. Mutation of seven single residues corresponding to those found in the active site of yeast exopolyphosphatase led to a severe decrease in h-prune activity, whereas one variant enzyme exhibited enhanced activity. Our results collectively suggest that prune is the missing exopolyphosphatase in animals and support the hypothesis that the metastatic effects of h-prune are modulated by inorganic polyphosphates, which are increasingly recognized as critical regulators in cells. 相似文献
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Antonio Naranjo Tuulikki Sokka Miguel A Descalzo Jaime Calvo-Alén Kim H?rslev-Petersen Reijo K Luukkainen Bernard Combe Gerd R Burmester Joe Devlin Gianfranco Ferraccioli Alessia Morelli Monique Hoekstra Maria Majdan Stefan Sadkiewicz Miguel Belmonte Ann-Carin Holmqvist Ernest Choy Recep Tunc Aleksander Dimic Martin Bergman Sergio Toloza Theodore Pincus the QUEST-RA Group 《Arthritis research & therapy》2008,10(2):R30