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101.
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Yali Xue Yuan Chen Qasim Ayub Ni Huang Edward?V. Ball Matthew Mort Andrew?D. Phillips Katy Shaw Peter?D. Stenson David?N. Cooper Chris Tyler-Smith the Genomes Project Consortium 《American journal of human genetics》2012,91(6):1022-1032
We have assessed the numbers of potentially deleterious variants in the genomes of apparently healthy humans by using (1) low-coverage whole-genome sequence data from 179 individuals in the 1000 Genomes Pilot Project and (2) current predictions and databases of deleterious variants. Each individual carried 281–515 missense substitutions, 40–85 of which were homozygous, predicted to be highly damaging. They also carried 40–110 variants classified by the Human Gene Mutation Database (HGMD) as disease-causing mutations (DMs), 3–24 variants in the homozygous state, and many polymorphisms putatively associated with disease. Whereas many of these DMs are likely to represent disease-allele-annotation errors, between 0 and 8 DMs (0–1 homozygous) per individual are predicted to be highly damaging, and some of them provide information of medical relevance. These analyses emphasize the need for improved annotation of disease alleles both in mutation databases and in the primary literature; some HGMD mutation data have been recategorized on the basis of the present findings, an iterative process that is both necessary and ongoing. Our estimates of deleterious-allele numbers are likely to be subject to both overcounting and undercounting. However, our current best mean estimates of ∼400 damaging variants and ∼2 bona fide disease mutations per individual are likely to increase rather than decrease as sequencing studies ascertain rare variants more effectively and as additional disease alleles are discovered. 相似文献
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David Chiszar Barbara O'Connell Robin Greenlee Bela Demeter Trooper Walsh Joan Chiszar Katy Moran Hobart M. Smith 《Zoo biology》1985,4(3):291-294
Rattlesnakes typically strike and release adult rodent prey. Striking is followed by a sustained, high rate of tongue flicking that guides the snake to the envenomated, dead prey. Wild-caught rattlesnakes exhibited this chemosensory searching for about 2.5 h, and the present study demonstrated that long-term captive rattlesnakes (Crotalus atrox, C durissus, C horridus, C vegrandis, C unicolor) at three zoos did the same. Because these zoo-raised snakes had always been offered dead rodents and because the snakes had become accustomed to ingesting them without striking, the present snakes had rarely exercised their innate predatory repertoires. The duration of chemosensory searching in these snakes indicates that this important aspect of the predatory repertoire had not been degraded as a consequence of long-term captive husbandry. 相似文献
104.
Efficient insertional mutagenesis in lactococci and other gram-positive bacteria. 总被引:27,自引:5,他引:22
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In lactococci, the study of chromosomal genes and their regulation is limited by the lack of an efficient transposon mutagenesis system. We associated the insertion sequence ISS1 with the thermosensitive replicon pG+ host to generate a mutagenic tool that can be used even in poorly transformable strains. ISS1 transposition is random in different lactococcal strains as well as in Enterococcus faecalis and Streptococcus thermophilus. High-frequency random insertion (of about 1%) obtained with this system in Lactococcus lactis allows efficient mutagenesis, with typically one insertion per cell. After ISS1 replicative transposition, the chromosome contains duplicated ISS1 sequences flanking pG+ host. This structure allows cloning of the interrupted gene. In addition, efficient excision of the plasmid leaves a single ISS1 copy at the mutated site, thus generating a stable mutant strain with no foreign markers. Mutants obtained by this transposition system are food grade and can thus be used in fermentation processes. 相似文献
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Intrapopulation genomics in a model mutualist: Population structure and candidate symbiosis genes under selection in Medicago truncatula
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Michael A. Grillo Stephane De Mita Patricia V. Burke Kathryn L. S. Solórzano‐Lowell Katy D. Heath 《Evolution; international journal of organic evolution》2016,70(12):2704-2717
Bottom‐up evolutionary approaches, including geographically explicit population genomic analyses, have the power to reveal the mechanistic basis of adaptation. Here, we conduct a population genomic analysis in the model legume, Medicago truncatula, to characterize population genetic structure and identify symbiosis‐related genes showing evidence of spatially variable selection. Using RAD‐seq, we generated over 26,000 SNPs from 191 accessions from within three regions of the native range in Europe. Results from STRUCTURE analysis identify five distinct genetic clusters with divisions that separate east and west regions in the Mediterranean basin. Much of the genetic variation is maintained within sampling sites, and there is evidence for isolation by distance. Extensive linkage disequilibrium was identified, particularly within populations. We conducted genetic outlier analysis with FST‐based genome scans and a Bayesian modeling approach (PCAdapt). There were 70 core outlier loci shared between these distinct methods with one clear candidate symbiosis related gene, DMI1. This work sets that stage for functional experiments to determine the important phenotypes that selection has acted upon and complementary efforts in rhizobium populations. 相似文献
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