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排序方式: 共有661条查询结果,搜索用时 31 毫秒
101.
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Hersh CP DeMeo DL Raby BA Litonjua AA Sylvia JS Sparrow D Reilly JJ Silverman EK 《COPD》2006,3(4):189-194
Genome-wide linkage analysis in the Boston Early-Onset Chronic Obstructive Pulmonary Disease (COPD) Study has demonstrated significant evidence of linkage to chromosome 8p for forced expiratory volume in 1 second, an important COPD-related phenotype. In this study, we sought to fine map the linkage peak and to test variants in two candidate genes for association with COPD and related traits. In a variance component linkage analysis on chromosome 8, including seven additional short tandem repeat markers, the logarithm of the odds of linkage score was reduced from 3.30 to 1.80 (at 1 cM). Five single nucleotide polymorphisms (SNPs) in Defensin Beta-1 (DEFB1) were genotyped in the Boston Early-Onset COPD Study families; none was significantly associated. Four SNPs and an insertion-deletion polymorphism in Macrophage Scavenger Receptor-1 (MSR1) were also genotyped in the family-based study. A coding variant (Pro275Ala) was marginally associated with two qualitative airflow obstruction traits (p < or = 0.02). This SNP showed a trend toward association in a case-control study comparing participants in the National Emphysema Treatment Trial to smoker controls (p = 0.07). Despite the reduced support for linkage upon further analysis, it remains possible that chromosome 8p contains a gene that influences COPD susceptibility. There is marginal, though not convincing, evidence for association with MSR1. 相似文献
103.
R Alexander A Kerby AA Aubdool AR Power S Grover C Gentry AD Grant 《British journal of pharmacology》2013,168(3):761-772
Background and Purpose
The Ca2+-permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (–/–) mice, and the increases in [Ca2+]i produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF.Experimental Approach
Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca2+ concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists.Key Results
Administration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and –/– mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca2+]i in neurons from +/+ and –/– mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca2+ in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF.Conclusions and Implications
TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist. 相似文献104.
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Cho MH Castaldi PJ Wan ES Siedlinski M Hersh CP Demeo DL Himes BE Sylvia JS Klanderman BJ Ziniti JP Lange C Litonjua AA Sparrow D Regan EA Make BJ Hokanson JE Murray T Hetmanski JB Pillai SG Kong X Anderson WH Tal-Singer R Lomas DA Coxson HO Edwards LD MacNee W Vestbo J Yates JC Agusti A Calverley PM Celli B Crim C Rennard S Wouters E Bakke P Gulsvik A Crapo JD Beaty TH Silverman EK;ICGN Investigators;ECLIPSE Investigators;COPDGene Investigators 《Human molecular genetics》2012,21(4):947-957
The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study. Genotyping was performed on Illumina platforms with additional markers imputed using 1000 Genomes data; results were summarized using fixed-effect meta-analysis. We identified a new genome-wide significant locus on chromosome 19q13 (rs7937, OR = 0.74, P = 2.9 × 10(-9)). Genotyping this single nucleotide polymorphism (SNP) and another nearby SNP in linkage disequilibrium (rs2604894) in 2859 subjects from the family-based International COPD Genetics Network study (ICGN) demonstrated supportive evidence for association for COPD (P = 0.28 and 0.11 for rs7937 and rs2604894), pre-bronchodilator FEV(1) (P = 0.08 and 0.04) and severe (GOLD 3&4) COPD (P = 0.09 and 0.017). This region includes RAB4B, EGLN2, MIA and CYP2A6, and has previously been identified in association with cigarette smoking behavior. 相似文献
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希—内学习能力测验在中国聋儿中使用的信度和效度 总被引:4,自引:0,他引:4
采用经部分修改的希-内学习能力测验(H-NTLA)量表对全国21个省、市、自治区1758名3-17岁聋儿逐人测试。样本人群地区分布、家长职业构成与1990年全国人口普查资料一致。1758名聋儿智商呈现正态分布(g1=0.011P>0.05,g2=0.058P>0.05)。测试员间信度系数0.981(N=24),复测信度0.841(N=136),分半信度0.927(3-8岁)及0.854(9-17岁)。各分测验得分随年龄增加而增加,小年龄组增加明显,大年龄组增加缓慢。各分测验之间、各分测验和总离差智商之间大多数相关系数有显著统计学意义。智商与学习成绩(语文及数学)相关系数0.208(P<0.01N=224),与教师评语等级相关系数0.44(P<0.05df=16),表明经修订的H-NTLA量表适用于中国听力语言障碍人群进行智力评定。 相似文献
110.