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排序方式: 共有1121条查询结果,搜索用时 15 毫秒
1.
So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (P combined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; P combined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation.  相似文献   
2.
Precise estimations of molecular rates are fundamental to our understanding of the processes of evolution. In principle, mutation and evolutionary rates for neutral regions of the same species are expected to be equal. However, a number of recent studies have shown that mutation rates estimated from pedigree material are much faster than evolutionary rates measured over longer time periods. To resolve this apparent contradiction, we have examined the hypervariable region (HVR I) of the mitochondrial genome using families of Adélie penguins (Pygoscelis adeliae) from the Antarctic. We sequenced 344 bps of the HVR I from penguins comprising 508 families with 915 chicks, together with both their parents. All of the 62 germline heteroplasmies that we detected in mothers were also detected in their offspring, consistent with maternal inheritance. These data give an estimated mutation rate (μ) of 0.55 mutations/site/Myrs (HPD 95% confidence interval of 0.29–0.88 mutations/site/Myrs) after accounting for the persistence of these heteroplasmies and the sensitivity of current detection methods. In comparison, the rate of evolution (k) of the same HVR I region, determined using DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period, was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17). Importantly, the latter rate is not statistically different from our estimate of the mutation rate. These results are in contrast to the view that molecular rates are time dependent.  相似文献   
3.
Primary open angle glaucoma (POAG) is a complex disease and is one of the major leading causes of blindness worldwide. Genome-wide association studies have successfully identified several common variants associated with glaucoma; however, most of these variants only explain a small proportion of the genetic risk. Apart from the standard approach to identify main effects of variants across the genome, it is believed that gene-gene interactions can help elucidate part of the missing heritability by allowing for the test of interactions between genetic variants to mimic the complex nature of biology. To explain the etiology of glaucoma, we first performed a genome-wide association study (GWAS) on glaucoma case-control samples obtained from electronic medical records (EMR) to establish the utility of EMR data in detecting non-spurious and relevant associations; this analysis was aimed at confirming already known associations with glaucoma and validating the EMR derived glaucoma phenotype. Our findings from GWAS suggest consistent evidence of several known associations in POAG. We then performed an interaction analysis for variants found to be marginally associated with glaucoma (SNPs with main effect p-value <0.01) and observed interesting findings in the electronic MEdical Records and GEnomics Network (eMERGE) network dataset. Genes from the top epistatic interactions from eMERGE data (Likelihood Ratio Test i.e. LRT p-value <1e-05) were then tested for replication in the NEIGHBOR consortium dataset. To replicate our findings, we performed a gene-based SNP-SNP interaction analysis in NEIGHBOR and observed significant gene-gene interactions (p-value <0.001) among the top 17 gene-gene models identified in the discovery phase. Variants from gene-gene interaction analysis that we found to be associated with POAG explain 3.5% of additional genetic variance in eMERGE dataset above what is explained by the SNPs in genes that are replicated from previous GWAS studies (which was only 2.1% variance explained in eMERGE dataset); in the NEIGHBOR dataset, adding replicated SNPs from gene-gene interaction analysis explain 3.4% of total variance whereas GWAS SNPs alone explain only 2.8% of variance. Exploring gene-gene interactions may provide additional insights into many complex traits when explored in properly designed and powered association studies.  相似文献   
4.
Sea trout are the sea-going migratory form of the freshwater brown trout (Salmo trutta L.) and since 1989 there have been marked declines in their stocks on the west coasts both of Scotland and Ireland. Various factors have been attributed as possible causal agents in these stock declines, including fresh water acidification, overfishing, climatic fluctuations, habitat degradation and sea lice parasitic burdens. The putative impact of infestations of sea trout by the ectoparasitic copepod sea louse, Lepeophtheirus salmonis (Krøyer), has featured prominently in the controversy, especially with regard to the role of inshore commercial salmon farms as a possible source of infestation of wild salmonids by sea lice. This study focused on the population genetics of L. salmonis around the coasts of Scotland: We sampled fish from wild and cultured stocks and included salmon (Salmo salar L.), rainbow trout (Oncorhynchus mykiss Walbaum) and sea trout as host species. Analyses of allozyme variation of sea lice were confined to data for two polymorphic loci (Fum, Got-2) and conformed to our initial expectation — that the inclusion of a planktonic larval phase in the life cycle of the copepod, in addition to the high mobility of the host fish, would enhance gene flow and preclude genetic differentiation of L. salmonis populations as a result of random drift alone. DNA polymorphism was quantified by means of PCR and RAPD analysis. Six primers were screened for 16 samples (from wild and farmed salmon, wild sea trout and farmed rainbow trout) — including the east, north and west coasts of Scotland — and the data analyzed by AMOVA (Analysis of Molecular Variance). In contrast to the allozyme results, the RAPD analysis showed striking patterns of genetic differentiation around the coasts of Scotland. The overall pattern was one of genetic homogeneity of L. salmonis populations sampled from wild salmon and sea trout. All of the L. salmonis samples taken from farmed salmon and rainbow trout did, however, show highly significant levels of genetic differentiation, both between wild and farmed salmonids and among the various farms themselves. Evidence of high levels of small-scale spatial or temporal heterogeneity of RAPD marker band frequencies was shown for the one farm from which repeat samples (July and November, 1995) were analysed. Samples of sea lice taken from west coast wild sea trout subjected to RAPD analysis also revealed the occurrence of putative “farm markers” in some individual parasites, indicating that they had possibly originated from salmon farms.  相似文献   
5.
A major challenge for studying the role of sexual selection in divergence and speciation is understanding the relative influence of different sexually selected signals on those processes in both intra‐ and interspecific contexts. Different signals may be more or less susceptible to co‐option for species identification depending on the balance of sexual and ecological selection acting upon them. To examine this, we tested three predictions to explain geographic variation in long‐ versus short‐range sexual signals across a 3,500 + km transect of two related Australian field cricket species (Teleogryllus spp.): (a) selection for species recognition, (b) environmental adaptation and (c) stochastic divergence. We measured male calling song and male and female cuticular hydrocarbons (CHCs) in offspring derived from wild populations, reared under common garden conditions. Song clearly differentiated the species, and no hybrids were observed suggesting that hybridization is rare or absent. Spatial variation in song was not predicted by geography, genetics or climatic factors in either species. In contrast, CHC divergence was strongly associated with an environmental gradient supporting the idea that the climatic environment selects more directly upon these chemical signals. In light of recently advocated models of diversification via ecological selection on secondary sexual traits, the different environmental associations we found for song and CHCs suggest that the impact of ecological selection on population divergence, and how that influences speciation, might be different for acoustic versus chemical signals.  相似文献   
6.
Vegetation structure and plant species diversity of restoration sites are predicted to directly affect pollinator attraction, with potential impacts on gene flow, reproduction, genetic diversity of future generations, and ultimately restoration success. We compared Banksia attenuata R.Br. (Proteaceae) in a low species diversity restoration site and an adjacent natural remnant. We assessed fecundity genetic diversity in adult plants and their offspring, mating system parameters and pollen dispersal using paternity assignment. Results were compared to an earlier study of reproductive functionality within a high species diversity restoration site that was restored in a similar manner, enabling us to investigate any association between plant species diversity and fecundity. Seed set data indicated no significant differences between restored and adjacent natural sites; however, seed set data between restoration sites was significantly different (2.08 ± 0.39 and 6.89 ± 1.12, respectively). The mean number of fruits (follicles) per inflorescence was not significantly different between restoration sites. Genetic diversity of adult plants and their offspring were comparable in all sites. Higher allelic richness and genetic differentiation in one restored site reflected sourcing beyond local provenance. Low correlated paternity indicated high levels of multiple siring of seeds and paternity assignment demonstrated strong genetic connectivity between sites. Reproductive functionality, as measured by fecundity and genetic diversity in the offspring of B. attenuata, is resilient to low species diversity within a restored plant community. We consider our results in the context of establishing seed production areas (SPAs) that maximize the quantity and genetic quality of Banksia seeds for restoration.  相似文献   
7.
Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.  相似文献   
8.
E. Evans  K. Ritchie    R. Merkel 《Biophysical journal》1995,68(6):2580-2587
Adhesion and cytoskeletal structure are intimately related in biological cell function. Even with the vast amount of biological and biochemical data that exist, little is known at the molecular level about physical mechanisms involved in attachments between cells or about consequences of adhesion on the material structure. To expose physical actions at soft biological interfaces, we have combined an ultrasensitive transducer and reflection interference microscopy to image submicroscopic displacements of probe contact with a test surface under minuscule forces. The transducer is a cell-size membrane capsule pressurized by micropipette suction where displacement normal to the membrane under tension is proportional to the applied force. Pressure control of the tension tunes the sensitivity in operation over four orders of magnitude through a range of force from 0.01 pN up to the strength of covalent bonds (approximately 1000 pN)! As the surface probe, a microscopic bead is biochemically glued to the transducer with a densely-bound ligand that is indifferent to the test surface. Movements of the probe under applied force are resolved down to an accuracy of approximately 5 nm from the interference fringe pattern created by light reflected from the bead. With this arrangement, we show that local mechanical compliance of a cell surface can be measured at a displacement resolution set by structural fluctuations. When desired, a second ligand is bound sparsely to the probe for focal adhesion to specific receptors in the test surface. We demonstrate that monitoring fluctuations in probe position at low transducer stiffness enhances detection of molecular adhesion and activation of cytoskeletal structure.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
9.
10.
A procedure has been developed for transforming protoplasts of the novobiocin producing strain Streptomyces niveus at high frequency. This required the isolation of strains LH13 and LH20 defective in DNA restriction from the wild type (ATCC 19793) which is transformed at very low frequencies. The LH13 and LH20 derivatives were obtained by curing pIJ702 DNA from the few S. niveus transformed protoplasts obtained by transformation of the wild type with high concentrations of pIJ702 DNA. Protoplasts of S. niveus strains LH13 and LH20 produced about 10(6) transformants/micrograms DNA with modified pIJ702 DNA derived by replication in S. niveus. Unmodified DNA (derived from replication in S: lividans) from a series of pIJ101, SCP2 and pSN2-based derivatives, gave transformation frequencies in the range of 10(2)-10(3) transformants/micrograms DNA. Optimal conditions for the formation and transformation of S. niveus protoplasts are described.  相似文献   
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