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61.
DALDINIA CONCENTRICA ATTACKING THE WOOD OF FRAXINUS EXCELSIOR 总被引:1,自引:0,他引:1
62.
For nonnormal data we suggest a test of location based on a broader family of distributions than normality. Such a test will in a sense fall between the standard parametric and non parametric tests. We see that the Wald tests based on this family of distributions have some advantages over the score tests and that they perform well in comparison to standard parametric and nonparametric tests in a variety of situations. We also consider when and how to apply such tests in practice. 相似文献
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65.
McKerrecher D Allen JV Caulkett PW Donald CS Fenwick ML Grange E Johnson KM Johnstone C Jones CD Pike KG Rayner JW Walker RP 《Bioorganic & medicinal chemistry letters》2006,16(10):2705-2709
The optimisation of a series of glucokinase activators is described, including attempts to uncouple the relationship between potency and plasma protein binding, and to better understand the key pharmacokinetic properties of the series. The use of unbound clearance as an optimisation parameter facilitated the identification of GKA50, a compound which combines excellent potency and pharmacokinetics with good free drug levels and solubility, and exhibits in vivo efficacy at 1mg/kg po in an acute rat OGTT model. 相似文献
66.
Ikechi G. Okpechi Brian L. Rayner Lize van der Merwe Bongani M. Mayosi Adebowale Adeyemo Nicki Tiffin Rajkumar Ramesar 《PloS one》2010,5(2)
Background
Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.Methodology/Principal Findings
Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS- [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482). U43653Conclusions/Significance
These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans. 相似文献67.
The high rates of failure in oncology drug clinical trials highlight the problems of using pre-clinical data to predict the clinical effects of drugs. Patient population heterogeneity and unpredictable physiology complicate pre-clinical cancer modeling efforts. We hypothesize that gene networks associated with cancer outcome in heterogeneous patient populations could serve as a reference for identifying drug effects. Here we propose a novel in vivo genetic interaction which we call 'synergistic outcome determination' (SOD), a concept similar to 'Synthetic Lethality'. SOD is defined as the synergy of a gene pair with respect to cancer patients' outcome, whose correlation with outcome is due to cooperative, rather than independent, contributions of genes. The method combines microarray gene expression data with cancer prognostic information to identify synergistic gene-gene interactions that are then used to construct interaction networks based on gene modules (a group of genes which share similar function). In this way, we identified a cluster of important epigenetically regulated gene modules. By projecting drug sensitivity-associated genes on to the cancer-specific inter-module network, we defined a perturbation index for each drug based upon its characteristic perturbation pattern on the inter-module network. Finally, by calculating this index for compounds in the NCI Standard Agent Database, we significantly discriminated successful drugs from a broad set of test compounds, and further revealed the mechanisms of drug combinations. Thus, prognosis-guided synergistic gene-gene interaction networks could serve as an efficient in silico tool for pre-clinical drug prioritization and rational design of combinatorial therapies. 相似文献
68.
To understand the molecular characteristics of China human rabies vaccine strains, we report the full-length genome of the aG strain and present a comprehensive analysis of this strain and almost all available lyssavirus genomes (58 strains) from GenBank (as of Jan 6, 2011). It is generally considered that the G protein plays a predominant role in determining the pathogenicity of the virus, to this end we predicted the tertiary structure of the G protein of aG strain, CTN181 strain and wild type strain HN10 based on the crystal structure of Vesicular stomatitis virus (VSV) G. The predicted RABV G structure has a similar topology to VSV G and the ectodomain can be divided into 4 distinct domains DI — DIV. By mapping the characterized mutations to this structure between China vaccine strains and their close street strains, we speculate that the G303(P-H) mutations of CTN181 and HN10 causing DII 3D change may be associated with the II attenuated virulence in both strains. Specifically, the two signature mutations (G165P and G231P) in the aG strain are withinßsheets, suggesting that both sites are of structural importance. 相似文献
69.
Crimean-Congo hemorrhagic fever (CCHF) is a severe illness with high fatality. Cases are reported in several countries in
Africa, Europe, the Middle East, and Asia. Phylogenetic analyses based on the virus S (nucleocapsid), M (glycoprotein), and
L (polymerase) genome segments sequences indicate distinct geographic lineages exist but their specific genetic characteristics
require elucidation. In this work we collected all full length S segment sequences and generated a phylogenetic tree based
on the alignment of these 62 samples. We then analyzed the alignment using entries from AAIndex, the Amino Acid Index database,
to identify amino acid mutations that performed significant changes in charge, pka, hydropathy and side chain volume. Finally,
we mapped these changes back to the tree and alignment to identify correlated mutations or sites that characterized a specific
lineage. Based on this analysis we are able to propose a number of sites that appear to be important for virus function and
which would be good candidates for experimental mutational analysis studies. 相似文献
70.
Arianna Manunza Joaquim Casellas Raquel Quintanilla Rayner González-Prendes Ramona N Pena Joan Tibau Anna Mercadé Anna Castelló Nitdia Aznárez Jules Hernández-Sánchez Marcel Amills 《BMC genomics》2014,15(1)