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41.
A retrospective study was performed to estimate the frequency of alloimmunization against red cell (RBC) antigens in a multiply transfused group. Patients (n = 186) were studied who had received at least six blood transfusions during a period of at least 3 months. Some 6944 units of blood were transfused. One hundred forty patients had hematologic disorders. The patients' sera were investigated every 3 months with indirect antiglobulin tests and enzyme-treated RBCs. Twenty-two patients (11.8%) made 33 antibodies. Seven patients made more than one antibody. Eight of the 22 patients (36.4%) made their first antibody before or at the 10th transfusion. The risk of immunization increased with the number of transfusions. Influence of gender and age was not demonstrable. Nor was a relationship demonstrated between blood transfusion reactions and RBC antibody formation; no delayed hemolytic transfusion reactions occurred. Anti-E was demonstrated in 12 patients and anti-K in 15. When the gene frequencies were taken into account, it appeared that anti-E was made by 11.5 percent of E-negative patients, most of whom were immunized after an estimated three transfusions with E-positive blood. Anti-K was made by 8.7 percent of the K-negative patients, after an estimated 2.1 units of K-positive blood. It might be desirable to match red cell units for the E and K antigens in patients at relatively high risk. These are primarily patients who have already formed an antibody and are going to receive many transfusions and women of childbearing age who are to receive more than 4 units of blood. 相似文献
42.
43.
The NADPH-dependent reduction of chromium (VI), a known carcinogen, by
hepatic microsomes was very similar for all five humans examined, with an
apparent Km for chromate of 1.04-1.68 microM, and a Vmax of 10.4- 10.7
nmol/min/mg protein. Inhibitor studies indicate no role for cytochrome
P450s, but a prominent role for flavoproteins, which could include P450
reductase, flavin-containing mono-oxygenase and cytochrome b5. Relative to
anaerobic conditions, Cr(VI) reduction was inhibited only 26-37% by room
air, which indicates that human microsomal Cr(VI) reduction could still
proceed at significant rates, even in tissues with high O2 tensions.
Studies with lung microsomes from one human exhibited Vmax and Km values
that were two-thirds lower and 2.8-fold greater, respectively, than those
of hepatic microsomes from the same individual; other Cr(VI)-reducing
parameters were similar for lung and liver. Various forms of exogenous
iron, when present at 0.76-6.3 microM, markedly enhanced both liver and
lung microsomal rates and Vmax of Cr(VI) reduction, but did not
significantly alter the other Cr(VI)- reducing parameters (Km, effects of
O2 and inhibitors). These iron levels were 3.1- to 26-fold lower than the
initial Cr(VI) concentration, which suggests that iron is serving a
catalytic role. The ratio of human microsomal Cr(VI) reduction rates under
aerobic versus anaerobic conditions remained fairly constant, regardless of
iron concentration. Small increases in intracellular iron could therefore
lead to large increases in the rate and extent of microsomal Cr(VI)
reduction. Individuals that are simultaneously exposed to Cr(VI) and to
agents that increase intracellular iron could therefore be at potentially
greater risk for Cr(VI) toxicity and carcinogenicity.
相似文献
44.
TEELUCKSINGH S; STEER CR; THOMPSON CJ; SECKL JR; DOUGLAS NJ; EDWARDS CRW 《QJM : monthly journal of the Association of Physicians》1991,78(2):185-190
We describe a young man who developed extensive hypothalamicdysfunction including diabetes insipidus, adipsia, hyperprolactinaemia,and poikiliothermia together with central sleep apnoea followingexposure to toluene. 相似文献
45.
CR Valeri G Ragno LE Pivacek R Srey JR Hess LE Lippert F Mettille R Fahie EM O''Neill IO Szymanski 《Transfusion》2002,42(12):1618-1618
46.
小鼠Nanog基因的克隆及对人宫颈癌上皮细胞的作用 总被引:1,自引:0,他引:1
目的:克隆小鼠Nanog基因并构建带绿色荧光蛋白的真核表达载体pG-Nanog,观察其对人宫颈癌上皮细胞(Hela细胞)中的表达,旨在为进一步观察其对成体细胞的表型变化及细胞增殖奠定前期实验学基础。方法:实验于2006-03/09在西北农林科技大学陕西省干细胞研究中心完成。Nanog基因的克隆参照庄淑珍的方法。Nanog基因真核表达载体的构建参照GeneBank中的小鼠Nanog基因序列,以pNA992为模板扩增Nanog基因,PCR产物以BglⅡ和SacⅡ双酶切,同时将pEGFP-C1用BglⅡ和SacⅡ鉴定,将该质粒命名为pG-Nanog。Hela细胞用含10%新生牛血清的Dulbecco’s改良培养基(Dulbecco’sModifiedEagleMedium,DMEM)培养,转染Hela细胞。转染前1d,在6孔板的每个孔中接种1.2×105个细胞,待细胞生长至60%~70%汇合时,取pG-Nanog与空载体各4μg分别加入500μL无血清无抗生素的DMEM培养液中,同时将6μL稀释于500μL无血清无抗生素的DMEM(干粉)培养液中,将两者混合,室温静置20min,将复合物加入到细胞中,置37℃,体积分数0.05的CO2培养箱中转染24h后吸出复合物加入完全培养基,48h后观察荧光。合成内源对照β-actin,收集转染4d后的细胞提取RNA,反转录为cDNA,然后分别扩增Nanog基因和β-actin基因。采用RT-PCR的方法检测Hela细胞中Nanog基因的表达。结果:①pEGFP-C1载体经双酶切后获得约1kbp的Nanog基因真核表达载体片段,同预期结果相一致,测序结果同GeneBank中的序列同源性达到99.7%。②将转染48h后的Hela细胞置于荧光显微镜下观察,可见明显的荧光,转染pG-Nanog的细胞绿色荧光蛋白集中于细胞核,将转染4d后Hela细胞的总RNA进行RT-PCR检测,产物经琼脂糖电泳分析,只有转染pG-Nanog的细胞中才能够检测到Nanog基因的相应条带。③转染48h后,对细胞进行抗增殖细胞核抗原免疫组化染色,未转染细胞和转染空质粒细胞及转染pG-Nanog细胞染色结果均呈阳性,转染了pG-Nanog的Hela细胞与正常细胞和转染空载体的细胞相比细胞形态发生了一定的改变,细胞表面形成了许多突起。结论:小鼠Nanog基因的克隆、真核表达载体的构建及在Hela细胞中的表达均获得成功,并观察到Hela细胞发生了形态的改变。 相似文献
47.
PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1 总被引:1,自引:0,他引:1
Kumar P Schelle MW Jain M Lin FL Petzold CJ Leavell MD Leary JA Cox JS Bertozzi CR 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(27):11221-11226
Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. A diacylated intermediate in SL-1 biosynthesis, SL(1278), has been shown to activate the adaptive immune response in human patients. Although several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL(1278) and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Here we demonstrate that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL(1278) and are essential for SL-1 biosynthesis. In vitro, recombinant PapA2 converts T2S to 2'-palmitoyl T2S, and PapA1 further elaborates this newly identified SL-1 intermediate to an analog of SL(1278). Disruption of papA2 and papA1 in M. tuberculosis confirmed their essential role in SL-1 biosynthesis and their order of action. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. The loss of SL-1 (and SL(1278)) did not appear to affect bacterial replication or trafficking, suggesting that the functions of SL-1 are specific to human infection. 相似文献
48.
Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications 总被引:1,自引:0,他引:1
Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y1 , P2Y12 , CYP2C9, CYP3A4 and CYP3A5 genotypes. 相似文献
49.
Sungwook Chung Seong-Ho Shin Carolyn R. Bertozzi James J. De Yoreo 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(38):16536-16541
The importance of nonclassical, multistage crystallization pathways is increasingly evident from theoretical studies on colloidal systems and experimental investigations of proteins and biomineral phases. Although theoretical predictions suggest that proteins follow these pathways as a result of fluctuations that create unstable dense-liquid states, microscopic studies indicate these states are long-lived. Using in situ atomic force microscopy to follow 2D assembly of S-layer proteins on supported lipid bilayers, we have obtained a molecular-scale picture of multistage protein crystallization that reveals the importance of conformational transformations in directing the pathway of assembly. We find that monomers with an extended conformation first form a mobile adsorbed phase, from which they condense into amorphous clusters. These clusters undergo a phase transition through S-layer folding into crystalline clusters composed of compact tetramers. Growth then proceeds by formation of new tetramers exclusively at cluster edges, implying tetramer formation is autocatalytic. Analysis of the growth kinetics leads to a quantitative model in which tetramer creation is rate limiting. However, the estimated barrier is much smaller than expected for folding of isolated S-layer proteins, suggesting an energetic rationale for this multistage pathway. 相似文献
50.