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101.
Tarner IH Nakajima A Seroogy CM Ermann J Levicnik A Contag CH Fathman CG 《Clinical immunology (Orlando, Fla.)》2002,105(3):304-314
Rheumatoid arthritis (RA) is an autoimmune arthritis, for which treatment options remain limited. This study investigated the potential role of adoptive cellular gene therapy as a novel means for treating the RA animal model collagen-induced arthritis (CIA). Adoptive transfer of antigen-specific T-cell hybridomas retrovirally transduced to express IL-4 1 day before booster immunization significantly reduced the number of inflamed joints. Cell transfer after clinical onset of disease had no therapeutic effect. Bioluminescence imaging showed that the hybridomas migrated to the inflamed joints, thus delivering the regulatory protein locally at the site of inflammation. The homing was, at least in part, due to chemotaxis in response to proinflammatory chemokines that are expressed in inflamed joints. There were no significant changes in the cytokine milieu of the draining lymph nodes, nor in the systemic levels of anti-collagen antibodies in treated mice. We conclude that the beneficial clinical effects observed in our model were most likely based on the local action(s) of IL-4 in the inflamed joints and that the local delivery (and effects) of regulatory cytokines, like IL-4, constitutes a novel and effective method of preventing organ-specific autoimmune disease and of minimizing systemic adverse effects. 相似文献
102.
79例广东汉族人群HLA-Cw及其KIR分析 总被引:2,自引:0,他引:2
目的:了解HLA—Cw与相应刺激性KIR(杀伤细胞免疫球蛋白样受体)和抑制性KIR在广东汉族人群中的分布。方法:对79例广东汉族骨髓移植供者,以DNA技术检测HLA-Cw和KIR表型。根据对KIR识别的特异性,将HLA-Cw分为HLA-Cw^lys.HLA-Cw^asn,分析个体HLA-Cw与相应刺激性或抑制性KIR的识别情况。结果:本组人群中,HLA-Cw^lys、HLA-Cw^asn的频率分别为26.6%、97.5%。表达KIR2DL1而无栩应配体者62.0%,表达2DS1而无相应配体者15.1%。27.8%表达HLA-Cw^asn而不表达相应KIR。25.3%、55.6%有抑制性HLA-Cw^lys或HLA-Cw^asn配体受体对,1.3%和14.0%的个体单独表达刺激性HLA-Cw^lys扣或HLA-Cw^asn配体受体对。15.1%的个体表达KIR2DS1而不表达HLA-Cw^lys。结论:在广东汉族人群中,存在KIR表型与自身HIA表型分离现象。抑制性HIA-Cw-KIR配对表达高于刺激性配对,约1/5单独表达刺激性HLA-Cw—KIR配对。 相似文献
103.
Reciprocal effects of apolipoprotein E alleles (ε2 AND ε4) on plasma lipid levels in normolipidemic subjects 总被引:2,自引:0,他引:2
A significantly lower frequency of the epsilon 2 allele and a significantly higher frequency of the epsilon 3 allele were found in the normolipidemic Japanese population than those in the normolipidemic Caucasian populations. We have compared plasma lipid variables among the apolipoprotein (apo) E phenotype groups and estimated the average effects of the three common alleles (epsilon 2, epsilon 3 and epsilon 4) on plasma lipid levels in normolipidemic subjects. Plasma triglyceride (TG), very low density lipoprotein (VLDL)-TG, VLDL-cholesterol (C) and apo E levels were high in the apo E3/2 group, intermediate in the apo E3/3 group and low in the apo E4/3 group, whereas plasma total cholesterol (TC), low density lipoprotein (LDL)-C and high density lipoprotein (HDL)-C levels were low in the apo E3/2 group, intermediate in the apo E3/3 group and high in the apo E4/3 group. Furthermore, the epsilon 2 allele had an effect to increase the TG, VLDL-TG, VLDL-C and apo E levels and decrease the TC, LDL-C and HDL-C levels, whereas the epsilon 4 allele had an effect opposite to the epsilon 2 allele. These results indicate that the epsilon 2 and epsilon 4 alleles have the reciprocal effects on plasma lipid, lipoprotein and apo E levels. 相似文献
104.
用分子克隆技术构建D12S391基因座等位基因分型标准物及群体遗传学研究 总被引:9,自引:1,他引:9
目的 解决长期困扰短串联重复序列(short tandem repeat,STR)分型上存在的准确性和标准化问题。方法 先用PCR扩增出D12S391基因座的9个等位基因片段,将其插入pUC重组质粒中,经DNA测序分析证实插入片段的结构及大小,用国际标准将插入的等位基因片段进行命名,最后经转染、扩大培养、扩增及再鉴定后,制备出标准的D12S391等位基因分型标准物。结果 应用此法制备出大量的D12S391基因座等位基因分型标准物,并将其用于调查该基因座在德国Mainz地区、日本Miyazaki地区及中国成都汉族、北京汉族、新疆维吾尔族和甘肃回族6个群体中的基因型分布频率。D12S391基因座在各群体中均有较高的多态性,其非父排除概念及个人识别能力分别为0.609-0.786和0.940-0.952。结论 该法制备的STR基因座等位基因分型标准物在法医科学实践中应用价值极高,D12S391基因座是一个非常适合于群体遗传学研究和法医科学应用的遗传标记。 相似文献
105.
Stature estimation based on hand length and foot length 总被引:1,自引:0,他引:1
Sanli SG Kizilkanat ED Boyan N Ozsahin ET Bozkir MG Soames R Erol H Oguz O 《Clinical anatomy (New York, N.Y.)》2005,18(8):589-596
This study was carried out to estimate the relationship between hand length, foot length and stature using multiple linear regression analyses based on a sample of male and female adult Turks residing in Adana. Measurements of hand length, foot length and stature were taken from 155 adult Turks (80 male, 75 female) aged 17-23 years. The participants were students of the Medical Faculty of Cukurova University. A multiple linear regression model was fitted to the observed data. Stature was taken as the response or dependent variable, hand length and foot length were taken as explanatory variables or regressors. All possible (simple and multiple) linear regression models for each of males, females and both genders together were tested for the best model. The multiple linear regression model for both genders together was found to be the best model with the highest values for the coefficients of determination R2 = 0.861 and R2adjusted = 0.859, and multiple correlation coefficient R = 0.928. 相似文献
106.
Lisa M. Nakamura Barry Eng Forbes D. Porter John S. Waye 《American journal of medical genetics. Part A》2001,102(4):383-386
Smith‐Lemli‐Opitz syndrome (SLOS) is an inherited multiple malformation syndrome caused by enzymatic deficiency of 3β‐hydroxysterol‐Δ7‐reductase (DHCR7). SLOS is thought to be most common among European Caucasians, with an incidence of 1 in 20,000 to 1 in 30,000 births. To define the carrier rate and ethnic distribution of SLOS, we screened DNA samples from 2,978 unrelated individuals for the most common SLOS mutation (IVS8‐1G→C). Twenty‐four heterozygotes of the IVS8‐1G→C mutation were detected in 2,978 individuals of European Caucasian and Black backgrounds. For European Caucasians, the carrier rate for SLOS may be as high as 1 in 30, suggesting an incidence of 1 in 1,700 to 1 in 13,400. This high number is supported by the recent observation of newborn and prenatal incidence of 1 in 22,000 in the Caucasian population. Ours is the first report of the IVS8‐1G→C mutation in persons of African ancestry. Published 2001 Wiley‐Liss, Inc. 相似文献
107.
Lisa T. Nelson Sabita Rakshit Hanshi Sun Deneen M. Wellik 《Developmental dynamics》2008,237(11):3410-3416
Hox genes are crucial for body axis specification during embryonic development. Hoxa11 plays a role in anteroposterior patterning of the axial skeleton, development of the urogenital tract of both sexes, and proximodistal patterning of the limbs. Hoxa11 expression is also observed in the neural tube. Herein, we report the generation of a Hoxa11eGFP targeted knock‐in allele in mice in which eGFP replaces the first coding exon of Hoxa11 as an in‐frame fusion. This allele closely recapitulates the reported mRNA expression patterns for Hoxa11. Hoxa11eGFP can be visualized in the tail, neural tube, limbs, kidneys, and reproductive tract of both sexes. Additionally, homozygous mutants recapitulate reported phenotypes for Hoxa11 loss of function mice, exhibiting loss of fertility in both males and females. This targeted mouse line will prove useful as a vital marker for Hoxa11 protein localization during control (heterozygous) or mutant organogenesis. Developmental Dynamics 237:3410–3416, 2008. © 2008 Wiley‐Liss, Inc. 相似文献
108.
Advances in sequencing and genotyping technologies over the last decade have enabled geneticists to easily characterize genetic variation at the nucleotide level. Hundreds of genes harboring mutations associated with genetic disease have now been identified by positional cloning. Using variation at closely linked genetic markers, it is possible to predict the times in the past at which particular mutations arose. Such studies suggest that many of the rare mutations underlying human genetic disorders are relatively young. Studies of variation at genetic markers linked to particular mutations can provide insights into human geographic history, and historical patterns of natural selection and disease, that are not available from other sources. We review two approaches for estimating allele age using variation at linked genetic markers. A phylogenetic approach aims to reconstruct the gene tree underlying a sample of chromosomes carrying a particular mutation, obtaining a “direct” estimate of allele age from the age of the root of this tree. A population genetic approach relies on models of demography, mutation, and/or recombination to estimate allele age without explicitly reconstructing the gene tree. Phylogenetic methods are best suited for studies of ancient mutations, while population genetic methods are better suited for studies of recent mutations. Methods that rely on recombination to infer the ages of alleles can be fine‐tuned by choosing linked markers at optimal map distances to maximize the information available about allele age. A limitation of methods that rely on recombination is the frequent lack of a fine‐scale linkage map. Maximum likelihood and Bayesian methods for estimating allele age that rely on intensive numerical computation are described, as well as “composite” likelihood and moment‐based methods that lead to simple estimators. The former provide more accurate estimates (particularly for large samples of chromosomes) and should be employed if computationally practical. Hum Mutat 18:87–100, 2001. © 2001 Wiley‐Liss, Inc. 相似文献
109.
青岛地区D6S477等五个短串联重复序列基因座的遗传多态性研究 总被引:3,自引:0,他引:3
目的 了解D6S477等5个基因座在青岛地区汉族群体中基因型分布及等位基因频率等遗传多态性数据,初步探讨其应用价值。方法 收集200名青岛地区汉族无关个体的静脉血,ACD抗凝,采用Chelex法提取DNA,应用聚合酶链反应技术,扩增D6S477、D9S1118、D18S865、D19S400和D20S161基因座的短串联重复序列,聚丙烯酰胺凝胶垂直电泳,银染显色分型。结果 获得了青岛地区汉族群体上述5个基因座的等位基因频率,基因型分布均符合Hardy-Weinberg平衡(P〉0.05)。结论 这5个基因座在青岛地区汉族群体中有较高的非父排除率和个人识别机率,在遗传学研究中有较高的应用价值。 相似文献
110.