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31.
Leah Wetherill Dongbing Lai Emma C. Johnson Andrey Anokhin Lance Bauer Kathleen K. Bucholz Danielle M. Dick Ahmad R. Hariri Victor Hesselbrock Chella Kamarajan John Kramer Samuel Kuperman Jacquelyn L. Meyers John I. Nurnberger Jr Marc Schuckit Denise M. Scott Robert E. Taylor Jay Tischfield Bernice Porjesz Alison M. Goate Howard J. Edenberg Tatiana Foroud Ryan Bogdan Arpana Agrawal 《Genes, Brain & Behavior》2019,18(6)
Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk. 相似文献
32.
Presenilin function and gamma-secretase activity 总被引:1,自引:0,他引:1
Alzheimer's disease (AD) is the most common form of dementia and is characterized pathologically by the accumulation of beta-amyloid (Abeta) plaques and neurofibrillary tangles in the brain. Genetic studies of AD first highlighted the importance of the presenilins (PS). Subsequent functional studies have demonstrated that PS form the catalytic subunit of the gamma-secretase complex that produces the Abeta peptide, confirming the central role of PS in AD biology. Here, we review the studies that have characterized PS function in the gamma-secretase complex in Caenorhabditis elegans, mice and in in vitro cell culture systems, including studies of PS structure, PS interactions with substrates and other gamma-secretase complex members, and the evidence supporting the hypothesis that PS are aspartyl proteases that are active in intramembranous proteolysis. A thorough knowledge of the mechanism of PS cleavage in the context of the gamma-secretase complex will further our understanding of the molecular mechanisms that cause AD, and may allow the development of therapeutics that can alter Abeta production and modify the risk for AD. 相似文献
33.
Background
Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. 相似文献34.
Albart Coster John WM Bastiaansen Mario PL Calus Johan AM van Arendonk Henk Bovenhuis 《遗传、选种与进化》2010,42(1):9
The objective of this simulation study was to compare the effect of the number of QTL and distribution of QTL variance on the accuracy of breeding values estimated with genomewide markers (MEBV). Three distinct methods were used to calculate MEBV: a Bayesian Method (BM), Least Angle Regression (LARS) and Partial Least Square Regression (PLSR). The accuracy of MEBV calculated with BM and LARS decreased when the number of simulated QTL increased. The accuracy decreased more when QTL had different variance values than when all QTL had an equal variance. The accuracy of MEBV calculated with PLSR was affected neither by the number of QTL nor by the distribution of QTL variance. Additional simulations and analyses showed that these conclusions were not affected by the number of individuals in the training population, by the number of markers and by the heritability of the trait. Results of this study show that the effect of the number of QTL and distribution of QTL variance on the accuracy of MEBV depends on the method that is used to calculate MEBV. 相似文献
35.
36.
Kapoor M Wang JC Bertelsen S Bucholz K Budde JP Hinrichs A Agrawal A Brooks A Chorlian D Dick D Hesselbrock V Foroud T Kramer J Kuperman S Manz N Nurnberger J Porjesz B Rice J Tischfield J Xuei X Schuckit M Edenberg HJ Bierut LJ Goate AM 《PloS one》2012,7(3):e33513
Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28相似文献
37.
Fragmented and scrambled mitochondrial ribosomal RNA coding regions among green algae: a model for their origin and evolution 总被引:4,自引:1,他引:3
Mitochondrial ribosomal RNA coding regions in the only three green algal
taxa investigated to date are fundamentally different in that they are
continuous in Prototheca wickerhamii, but highly fragmented and scrambled
in Chlamydomonas reinhardtii and Chlamydomonas eugametos. To gain more
insight into the mode of evolution of fragmented and scrambled
mitochondrial ribosomal RNA (rRNA) genes within the green algal group, this
work (1) provides additional information on fragmentation patterns of
mitochondrial small- and large-subunit (SSU and LSU) rRNAs that strongly
supports the concept of a gradual increase in the extent of discontinuity
of mitochondrial rRNAs among chlorophycean green algae and (2) reports the
first example of fragmented and scrambled mitochondrial LSU rRNA coding
regions in a green algal taxon outside the Chlamydomonas group. The present
study (1) suggests that the scrambling of the mitochondrial rRNA coding
regions may have occurred early in the evolution of fragmented and
scrambled mitochondrial rRNA genes within the chlorophycean green algal
group, most likely in parallel with the fragmentation events, (2) proposes
recombination as a possible mechanism involved in the evolution of these
mitochondrial rRNA genes, and (3) presents a hypothetical pathway for
converting continuous mitochondrial rRNA genes into the highly fragmented
and scrambled rRNA coding regions of Chlamydomonas through a series of
recombinatorial events between short repeated sequences.
相似文献
38.
Jifeng Tang Samantha J Baldwin Jeanne ME Jacobs C Gerard van der Linden Roeland E Voorrips Jack AM Leunissen Herman van Eck Ben Vosman 《BMC bioinformatics》2008,9(1):374
Background
Simple Sequence Repeat (SSR) or microsatellite markers are valuable for genetic research. Experimental methods to develop SSR markers are laborious, time consuming and expensive. In silico approaches have become a practicable and relatively inexpensive alternative during the last decade, although testing putative SSR markers still is time consuming and expensive. In many species only a relatively small percentage of SSR markers turn out to be polymorphic. This is particularly true for markers derived from expressed sequence tags (ESTs). In EST databases a large redundancy of sequences is present, which may contain information on length-polymorphisms in the SSR they contain, and whether they have been derived from heterozygotes or from different genotypes. Up to now, although a number of programs have been developed to identify SSRs in EST sequences, no software can detect putatively polymorphic SSRs. 相似文献39.
Jeanine A Verbunt Henk AM Seelen Feljandro P Ramos Bernard HM Michielsen Wim L Wetzelaer Martine Moennekens 《BMC neurology》2008,8(1):7
Background
Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective. 相似文献40.