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31.
Defective expression of the apoptosis-inducing CD95 (Fas/APO-1) molecule on T and B cells in IDDM 总被引:2,自引:0,他引:2
C. Giordano R. De Maria G. Stassi M. Todaro P. Richiusa M. Giordano R. Testi A. Galluzzo 《Diabetologia》1995,38(12):1449-1454
Summary Triggering of CD95 (Fas/APO-1) cell surface receptors regulates the elimination of autoreactive T and B lymphocytes through a mechanism of cell suicide called apoptosis. Three different mutations involving CD95 or its ligand are responsible for induction of autoimmunity in susceptible mouse strains. To determine whether a defect involving the CD95 receptor is associated with human insulin-dependent diabetes mellitus (IDDM), we have studied the expression of CD95 on peripheral blood mononuclear cells from IDDM patients at different stages of the disease. Three-colour flow cytometry and mean fluorescence analysis showed that T and B lymphocytes from newly diagnosed IDDM and patients with long-standing disease, and subjects at high risk of developing the disease were highly defective in CD95 expression (p<0.001), whereas monocytes from all the groups studied expressed normal amounts of CD95 molecules on their cell surface. T-cell subset analysis showed that the impairment of CD95 expression in IDDM patients and high-risk subjects involved both CD3+ CD4+ (p<0.001) and CD3+ CD8+ cells (p range: <0.01–0.001), suggesting that this alteration concerns both helper and cytotoxic T cells. Moreover, after activation in vitro with anti-CD3 monoclonal antibody, T cells from newly diagnosed IDDM patients maintained a reduced CD95 expression during the entire cell culture period (24–72 h) in comparison to the control population (p<0.001). In conclusion, we found a reduced expression of the apoptosis-inducing CD95 receptor on T and B lymphocytes of individuals with clinical and preclinical IDDM. We hypothesize that this defective expression may impair the capacity of autoreactive lymphocytes to undergo CD95-mediated apoptosis, contributing to the lack of control on beta-cell specific B- and T-cell clones.Abbreviations MFI
Mean fluorescence intensity
- mAb
monoclonal antibody
- ICA
islet cell autoantibody
- IAA
insulin autoantibody
- PE
phycoerythrin
- FITC
fluorescein
- Per-CP
peridinid chlorophyll protein
- PBMC
peripheral blood mononuclear cells
- AICD
activation-induced cell death 相似文献
32.
Ana M. Calvo‐Maroto Rafael J. Perez‐Cambrodi Santiago Garcia‐Lazaro Teresa Ferrer‐Blasco Alejandro Cerviño 《Journal of Diabetes》2016,8(5):619-628
Diabetes mellitus is a metabolic disease with a considerable impact on healthcare owing to its increased prevalence and high mortality rate. Structural, morphological, and physiological changes in each of the ocular components have been described in detail. Autofluorescence has been described as a good indicator of metabolic activity. The aim of the present review is to provide an overview of ocular endogenous fluorophores in the cornea, the crystalline lens, and the retinal pigment epithelium, the effects of diabetes mellitus and therefore the potential of autofluorescence assessment for screening and monitoring changes in diabetic patients. 相似文献
33.
Xiaoqing Shi Bingjie Li Yingying Yuan Liyinghui Chen Yadi Zhang Meng Yang Junjie Wang Dongchun Qin 《Pathology, research and practice》2018,214(8):1142-1148
Purpose
The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer.Methods
All case-control research studies that determined a relationship between MPO and cervical cancer reported up until March 1, 2018 in PubMed, Web of Science, VIP, WanFang, and the CNKI Database were accessed and included. The strength of association was evaluated with pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). We used sensitivity analysis to detect the stability of our results, conducted Q-test to evaluate heterogeneity and applied Begg’s funnel plot and Egger’s test to investigate any publication bias among selected studies.Results
In this meta-analysis, we included 5 eligible studies in the final evaluation, which included 1125 patients with cervical cancer and 1150 cancer-free control patients. A potential association between the MPO ?463 G?>?A polymorphism and cervical cancer risk was observed (recessive model: OR?=?0.65, 95%, CI: 0.43–0.98, P?=?0.038; homozygous model: OR?=?0.65, 95%, CI: 0.43–0.99, P?=?0.045), which indicates that genotype AA reduces the risk of cervical cancer by 35% compared to GG/GA or GG genotypes in our results. A stratified analysis by ethnicity identified a significant correlation among Caucasian patients (recessive model: OR?=?0.57, 95%, CI: 0.34–0.95, P?=?0.029; homozygous model: OR?=?0.60, 95%, CI: 0.36–0.99, P?=?0.048) and a stratified analysis by source of control identified a significant correlation among population-based studies.Conclusions
Our results suggest that the presence of polymorphism, ?463 G?>?A in patients might offer them protection against cervical cancer. By implementing randomized case-control or cohort studies with larger sample sizes, the clinical significance of our results can be further strengthened and verified. 相似文献34.
Jian Dong Jiang Michael Schlesinger Henry Sacks Donna Mildvan Julia P. Roboz J. George Bekesi 《Journal of clinical immunology》1997,17(2):185-192
Apoptosis mediated via the CD95 (FAS/APO-1) receptor is thought to play a role in the depletion of CD4+ T cells in HIV infection. In the present study expression of the CD95 antigen on lymphocyte subsets and the plasma level of soluble CD95 (sCD95) were determined in HIV-1-infected adults. The expression of CD95 was increased on CD8 cells in all groups of HIV+ individuals, while increased expression of CD95+ cells on CD4 cells was limited to individuals with CD4 counts of <200 mm3. The proportion of CD4+ that expressed CD95 was inversely correlated with the percentage of CD4+ PBL. The concentration of sCD95 was significantly higher in the plasma of HIV-infected individuals than in normal controls. The level of sCD95 in HIV-infected subjects showed no correlation with the percentage of PBL expressing CD95, indicating that the increased level of sCD95 did not reflect release from CD95+ PBL. The plasma sCD95 concentration was significantly correlated with the percentage of CD8+ cells and, particularly, with CD8+CD38– cells. A striking inverse correlation was found between the sCD95 plasma concentration and the proportion of CD4+CD95+ cells out of the total CD4+ population. There was no correlation between the serum level of sCD95 and that of soluble CD8 (sCD8), both of which were increased in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals. Unlike the level of sCD95, the level of sCD8 in the plasma of HIV+ individuals was correlated with the percentage of CD95+ and CD8+CD38+ cells. The present study indicates that plasma sCD95 may be one of the factors that regulate apoptotic death of lymphocytes in HIV infection. 相似文献
35.
Eldering E Mackus WJ Derks IA Evers LM Beuling E Teeling P Lens SM van Oers MH van Lier RA 《European journal of immunology》2004,34(7):1950-1960
Various routes to apoptosis can be active during B cell development. In a model system of mature B cells, differences in caspase-3 processing have suggested that antigen receptor (BCR)-mediated apoptosis may involve a zVAD-insensitive initiator protease(s). In search of the events leading to caspase-3 activation, we now establish that both CD95- and BCR-mediated apoptosis depend on Bax activation and cytochrome C (cytC) release. Nevertheless, the timing and caspase-dependence of mitochondrial membrane depolarization differed considerably after CD95- or BCR-triggering. To delineate events subsequent to cytC release, we compared apoptosis induced via BCR triggering and via direct mitochondrial depolarization by CCCP. In both cases, partial processing of caspase-3 was observed in the presence of zVAD. By expression in 293 cells we addressed the potential of candidate initiator caspases to function in the presence of zVAD, and found that caspase-9 efficiently processed caspase-3, while caspase-2 or -8 were inactive. Finally, retroviral expression of dominant-negative caspase-9 inhibited both CD95- and BCR-mediated apoptosis. In conclusion, we obtained no evidence for involvement of a BCR-specific protease. Instead, our data show for the first time that the BCR-signal causes Bax translocation, followed by mitochondrial depolarization, and cytC release. Subsequent caspase-9 activation can solely account for events further downstream. 相似文献
36.
目的:基于突触可塑性观察电针曲池、足三里对大脑中动脉闭塞(MCAO)大鼠运动障碍的改善。方法:将60只雄性SD大鼠随机分为假手术组、模型组、穴位组、非穴组,每组15只。采用Zea Longa线拴法制备MCAO大鼠模型,电针曲池、足三里,干预14 d。通过神经功能评分判断大鼠的神经功能缺损情况;CatWalk步态分析比较各组大鼠运动功能,TTC染色观察脑梗死体积,透射电镜观察突触超微结构和数量,免疫荧光检测缺血侧运动皮层突触相关因子突触后致密物-95(PSD-95)、突触蛋白的表达情况。结果:干预14 d后,与模型组比较,穴位组大鼠神经功能评分降低(P<0.05);步行速度提高、双足支撑时间缩短(P<0.05);脑梗死体积减少(P<0.05);突触超微结构改善明显,突触数量增加(P<0.05),突触相关因子突触蛋白、PSD-95表达上调(P<0.05)。Catwalk步态参数、脑梗死体积与突触超微结构改善有一致性。结论:电针曲池、足三里穴可改善MCAO大鼠运动障碍,其机制可能与上调突触相关因子的表达,改善突触可塑性有关。 相似文献
37.
目的:观察姜黄素对AD模型APP/PS1双转基因小鼠突触相关蛋白突触后致密蛋白-95(postsynaptic densityprotein-95,PSD-95)和骨架蛋白Shank1表达的影响。方法:将3月龄的APP/PS1双转基因小鼠随机分为模型组、罗格列酮阳性对照组(10 mg.kg-1.d-1)、姜黄素高、中、低剂量组(400,200,100 mg.kg-1.d-1),正常对照组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Western blot方法进行检测。结果:行为学检测,治疗组与模型组相比定位航行实验和空间探索实验存在不同程度的差异(P<0.01或P<0.05)。PSD-95和Shank1免疫组化,模型组小鼠大脑海马CA1区较对照组阳性细胞明显减少(P<0.01),姜黄素干预组有所恢复。Western blot检测海马PSD-95的蛋白结果显示,模型组小鼠海马PSD-95的蛋白表达条带均比对照组小鼠明显变细、颜色变浅(P<0.01);姜黄素干预组小鼠海马PSD-95的蛋白表达条带均明显增粗、颜色加深(P<0.05)。结论:姜黄素增加APP/PS1双转基因小鼠突触相关蛋白shank1和PSD-95表达,改善APP/PS1双转基因小鼠突触的结构和可塑性,提高空间学习记忆能力。 相似文献
38.
39.
Christine Zimmermann Marlies Rawiel Claudine Blaser Martina Kaufmann Hanspeter Pircher 《European journal of immunology》1996,26(12):2903-2910
The role of Fas in the homeostatic regulation of CD8+ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) αβ transgenes specific for the LCMV glycoprotein peptide aa 33–41 in the context of H-2Db were used. Five main results emerged: first, development of lymphadenopathy and of CD4−CD8− double-negative B220+ T cells in lpr mice was not inhibited by the αβ TCR transgenes; second, tolerance induction and peripheral deletion of CD8+ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8+ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8+ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4−CD8− double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8+ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas. 相似文献
40.
目的 探讨中药芪加真武汤联合糖皮质激素对系统性红斑狼疮(SLE)患者外周血淋巴细胞(PBL)凋亡及Fas、FasL表达的影响。方法 采用血清药理学方法 ,制取芪加真武汤含药兔血清。运用流式细胞仪检测19例SLE患者外周血淋巴细胞在不同浓度的芪加真武汤的含药血清(20%、10%、5%)、地塞米松(0.001mol/L)及两者联合刺激下细胞凋亡和Fas、FasL表达的变化。结果 ①SLE患者PBL凋亡率明显高于正常组(P<0.001),Fas表达明显多于正常组(P<0.01),FasL表达与正常组差异不明显(P>0.05)。②10%、20%含药血清显著减少SLE患者PBL的凋亡率(P<0.01),显著降低Fas表达(P<0.01),升高FasL的阳性细胞率(P<0.05);③地塞米松可增高SLE患者PBL的凋亡率(P<0.05),但对Fas、FasL的表达无影响(P>0.05);④含药血清联合地塞米松显著减少PBL凋亡率(P<0.01),降低Fas表达(P<0.05),明显升高FasL的阳性细胞率(P<0.01)。结论 SLE患者PBL存在凋亡及凋亡相关蛋白表达的紊乱,中药芪加真武汤在体外可纠正其紊乱,缓解由地塞米松引起的PBL过度凋亡。 相似文献