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101.
BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.  相似文献   
102.
Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8+ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8+ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8+ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8+ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8+ T cells to induce costimulation blockade-resistant allograft rejection.  相似文献   
103.
目的:探讨固本延衰方延缓亚急性衰老模型小鼠衰老的机制。方法:将60只小鼠随机分为4组,除正常对照组外均皮下注射D-半乳糖造成衰老模型,并给予不同剂量的固本延衰方治疗,分别用放免法及流式法测定脾淋巴细胞白细胞介素2及其受体水平。结果:衰老模型组IL-2及其受体水平明显低于正常对照组(P<0.05),固本延衰方各剂量组IL-2及其受体水平明显高于衰老模型组(P<0.05,P<0.01)。结论:提示固本延衰方通过提高衰老机体淋巴细胞IL-2及其受体表达水平,从而调节机体免疫功能延缓衰老。  相似文献   
104.
目的探讨影响乳腺癌患者预后的因素,协助临床制定手术方式及术后治疗方案。方法选择80例各型乳腺癌患者的标本,应用免疫组化SP方法,检测乳腺癌组织中癌基因BcL-2、Bax及黏附因子CD44V6的表达情况。结果乳腺癌中BcL-2、Bax及CD44V6的表达情况与肿瘤组织学分级、瘤体直径。有无转移及患者术后存活时间均有显著性相关(P<0.05或0.01)。结论BcL-2高表达、Bax低表达、CD44V6低表达的患者组织学分级好,肿瘤体积小,淋巴结转移少,术后存活时间长,这部分患者可做肿物扩大切除而保留乳房或即使已做乳房切除,术后也可减少放疗及化疗剂量。  相似文献   
105.
目的:研究重组人内皮细胞衍生的白细胞介素-8(IL8)对失血性休克的作用.方法:大鼠股动脉放血至MABP532kPa,维持90min,复制晚期失血性休克模型.输血后,静脉注射IL8250μg·kg-1.放免法测定血浆ET1和6KPGF1α含量.结果:给予IL8后,MABP显著提高,休克状态改善,2h存活率相应提高;休克晚期血浆ET1水平比正常明显升高(21±4vs82±18ng·L-1,P<001),血浆6KPGF1α含量明显降低(107±12vs157±11ng·L-1,P<001).IL8显著降低血浆ET1水平(10±4ng·L-1,P<001),提高血浆6KPGF1α含量(368±16ng·L-1,P<001).结论:IL8具有较好的抗休克作用.  相似文献   
106.
107.
6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B4 and thromboxane B2 production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.  相似文献   
108.
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A.  相似文献   
109.
依据乡村医生人力结构现状调查结果,就现阶段县级卫校在初级卫生保健中的作用及今后面向乡村医生办学的可行性作了具体的分析和探讨。结论是:提高质量,加强对在岗乡医进行系统化正规中专层次的职后复训,应是县级卫校今后1O年的最主要的任务。  相似文献   
110.
Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.  相似文献   
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