全文获取类型
收费全文 | 232篇 |
免费 | 14篇 |
专业分类
246篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 13篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 9篇 |
2014年 | 11篇 |
2013年 | 16篇 |
2012年 | 20篇 |
2011年 | 15篇 |
2010年 | 10篇 |
2009年 | 10篇 |
2008年 | 10篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 10篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 6篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 7篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有246条查询结果,搜索用时 0 毫秒
81.
Karim Gharbi Timothée Cézard Maxime Galan Anne Loiseau Marian Thomson Pierre Pudlo Carole Kerdelhué Arnaud Estoup 《Molecular ecology》2013,22(14):3766-3779
Molecular markers produced by next‐generation sequencing (NGS) technologies are revolutionizing genetic research. However, the costs of analysing large numbers of individual genomes remain prohibitive for most population genetics studies. Here, we present results based on mathematical derivations showing that, under many realistic experimental designs, NGS of DNA pools from diploid individuals allows to estimate the allele frequencies at single nucleotide polymorphisms (SNPs) with at least the same accuracy as individual‐based analyses, for considerably lower library construction and sequencing efforts. These findings remain true when taking into account the possibility of substantially unequal contributions of each individual to the final pool of sequence reads. We propose the intuitive notion of effective pool size to account for unequal pooling and derive a Bayesian hierarchical model to estimate this parameter directly from the data. We provide a user‐friendly application assessing the accuracy of allele frequency estimation from both pool‐ and individual‐based NGS population data under various sampling, sequencing depth and experimental error designs. We illustrate our findings with theoretical examples and real data sets corresponding to SNP loci obtained using restriction site–associated DNA (RAD) sequencing in pool‐ and individual‐based experiments carried out on the same population of the pine processionary moth (Thaumetopoea pityocampa). NGS of DNA pools might not be optimal for all types of studies but provides a cost‐effective approach for estimating allele frequencies for very large numbers of SNPs. It thus allows comparison of genome‐wide patterns of genetic variation for large numbers of individuals in multiple populations. 相似文献
82.
Bessadok A Garcia E Jacquet H Martin S Garrigues A Loiseau N André F Orlowski S Vivaudou M 《The Journal of biological chemistry》2011,286(5):3552-3569
ATP-sensitive K(+) (K(ATP)) channels are the target of a number of pharmacological agents, blockers like hypoglycemic sulfonylureas and openers like the hypotensive cromakalim and diazoxide. These agents act on the channel regulatory subunit, the sulfonylurea receptor (SUR), which is an ABC protein with homologies to P-glycoprotein (P-gp). P-gp is a multidrug transporter expressed in tumor cells and in some healthy tissues. Because these two ABC proteins both exhibit multispecific recognition properties, we have tested whether SUR ligands could be substrates of P-gp. Interaction with P-gp was assayed by monitoring ATPase activity of P-gp-enriched vesicles. The blockers glibenclamide, tolbutamide, and meglitinide increased ATPase activity, with a rank order of potencies that correlated with their capacity to block K(ATP) channels. P-gp ATPase activity was also increased by the openers SR47063 (a cromakalim analog), P1075 (a pinacidil analog), and diazoxide. Thus, these molecules bind to P-gp (although with lower affinities than for SUR) and are possibly transported by P-gp. Competition experiments among these molecules as well as with typical P-gp substrates revealed a structural similarity between drug binding domains in the two proteins. To rationalize the observed data, we addressed the molecular features of these proteins and compared structural models, computerized by homology from the recently solved structures of murine P-gp and bacterial ABC transporters MsbA and Sav1866. Considering the various residues experimentally assigned to be involved in drug binding, we uncovered several hot spots, which organized spatially in two main binding domains, selective for SR47063 and for glibenclamide, in matching regions of both P-gp and SUR. 相似文献
83.
Jianhua Wang Garry S. Hanan Frédérique Loiseau Sebastiano Campagna 《Inorganica chimica acta》2007,360(3):876-884
A new series of ruthenium(II) complexes, based on 4′-(9-anthryl)-2,2′:6′,2″-terpyridine (an-tpy), have been synthesized from the Ru(III) precursor (an-tpy)RuCl3 (4). These new Ru(II) complexes, [(an-tpy)Ru(tpy-pm-R)] (R = H, 3a; Cl, 3b; phenyl, 3c; p-bromophenyl, 3d), have extended π-conjugation through the 5′-substituted pyrimidyl group, and have been characterized by analytical and spectroscopic methods, and X-ray single crystal structure determination for 3b and 3d. Luminescence lifetime measurements have shown that the anthryl chromophore greatly increases room temperature (r.t.) excited-state lifetime, even though it is not directly connected to the ligand involved in the metal-to-ligand charge transfer (3MLCT) emitting state. This result demonstrates that an equilibrium is established between the anthryl triplet state (3an) and the 3MLCT state even though the two chromophores are physically separated by more than one nanometer. At low temperature in rigid matrix, such equilibrium does not take place and emission arises from both 3an and 3MLCT excited states. The temperature dependence of the excited-state equilibration induces a temperature switch from single (room temperature) to dual (77 K) emission behavior. 相似文献
84.
Various cationic lipophilic compounds can reverse the multidrug resistance of cancer cells. Possible interaction between these
compounds, which are known as modulators, has been assessed by measuring leakage of Sulphan blue from anionic liposomes, induced
both by verapamil alone and by verapamil in combination with diltiazem, quinine, thior idazine or clomipramine. An equation
was derived to quantify the permeation doses and Hill coefficients of the drugs and mixtures between them by simultaneous
fitting of the experimental data. The interaction was tested by two methods, the competition plot and the isobole method;
both showed synergy between verapamil and each of diltiazem, qui nine and thioridazine. The dose factor of potentiation for
verapamil determined within membranes was 4.0 ± 0.4 with diltiazem, 3.2 ± 0.4 with quinine and 2.4 ± 0.3 with thior idazine.
The results suggest that the effectiveness of reversing multidrug resistance may be increased with modulators such as verapamil
and diltiazem that have a much greater effect in combination than what would be expected from their effects when considered
separately. 相似文献
85.
Orianne Tournayre Jean‐Baptiste Pons Maxime Leuchtmann Raphael Leblois Sylvain Piry Ondine Filippi‐Codaccioni Anne Loiseau Jeanne Duhayer Inazio Garin Fiona Mathews Sbastien Puechmaille Nathalie Charbonnel Dominique Pontier 《Ecology and evolution》2019,9(21):12272-12290
The greater horseshoe bat (Rhinolophus ferrumequinum) is among the most widespread bat species in Europe but it has experienced severe declines, especially in Northern Europe. This species is listed Near Threatened in the European IUCN Red List of Threatened Animals, and it is considered to be highly sensitive to human activities and particularly to habitat fragmentation. Therefore, understanding the population boundaries and demographic history of populations of this species is of primary importance to assess relevant conservation strategies. In this study, we used 17 microsatellite markers to assess the genetic diversity, the genetic structure, and the demographic history of R. ferrumequinum colonies in the western part of its distribution. We identified one large population showing high levels of genetic diversity and large population size. Lower estimates were found in England and northern France. Analyses of clustering and isolation by distance suggested that the Channel and the Mediterranean seas could impede R. ferrumequinum gene flow. These results provide important information to improve the delineation of R. ferrumequinum management units. We suggest that a large management unit corresponding to the population ranging from Spanish Basque Country to northern France must be considered. Particular attention should be given to mating territories as they seem to play a key role in maintaining high levels of genetic mixing between colonies. Smaller management units corresponding to English and northern France colonies must also be implemented. These insular or peripheral colonies could be at higher risk of extinction in the near future. 相似文献
86.
Steve Horvath Yafeng Zhang Peter Langfelder René S Kahn Marco PM Boks Kristel van Eijk Leonard H van den Berg Roel A Ophoff 《Genome biology》2012,13(10):1-18
Background
Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues.Results
We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained.Conclusions
Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles. 相似文献87.
Condition-dependent effects of corticosterone on a carotenoid-based begging signal in house sparrows
Begging is a complex display involving a variety of different visual and auditory signals. Parents are thought to use these signals to adjust their investment in food provisioning. The mechanisms that ensure the honesty of begging displays as indicators of need have been recently investigated. It has been shown that levels of corticosterone (Cort), the hormone released during the stress response, increase during food shortage and are associated with an increased begging rate. In a recent study in house sparrows, although exogenous Cort increased begging rate, parents did not accordingly adjust their provisioning rate. Here, we tested the hypothesis that Cort might affect the expression of other components of begging displays, such as flange color (a carotenoid-based trait). We experimentally increased levels of circulating Cort and investigated the effects of the treatment on (1) the flange coloration of the nestlings, (2) the behavioral response and (3) the parental allocation of food and (4) nestling condition and cell-mediated immune response. We found that Cort affected flange coloration in a condition-dependent way. Cort-injected nestlings had less yellow flanges than controls only when in poor body condition. Parental feeding rate was also affected by the Cort treatment in interaction with flange color. Feeding rate of Cort-injected nestlings was negatively and significantly correlated with flange color (nestlings with yellower flanges receiving more food), whereas feeding rate and flange color were not correlated in control chicks. We also found that nestlings injected with Cort showed a weaker immune response than controls. These results suggest that, indeed, Cort has the potential to affect multiple components of the begging display. As Cort levels naturally raise during fasting, parents have to take into account these multiple components to take a decision as to optimally share their investment among competing nestlings. 相似文献
88.
We isolated and characterized 11 microsatellite loci in the grasshopper Oedaleus decorus (Orthoptera: Acrididae), an endangered species in Central Europe. Polymorphism was studied from two populations, one out of two populations known from Switzerland (n = 20 individuals) and one site from south of France (n = 20). The number of alleles and the expected heterozygosity ranged from five to 12 and from 0.559 to 0.898, respectively, in the Swiss population, and from 14 to 23 and from 0.895 to 0.974, respectively, in the French population. These microsatellite markers are suitable for further conservation genetic studies of O. decorus. 相似文献
89.
90.