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21.
K. Murata K. Fox-Talbot Z. Qian K. Takahashi G. L. Stahl W. M. Baldwin III B. A. Wasowska 《American journal of transplantation》2007,7(11):2605-2614
The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection. 相似文献
22.
转化生长因子-β和碱性成纤维细胞因子在儿童原发性局灶节段性肾小球硬化肾组织中的表达 总被引:1,自引:1,他引:0
目的:通过检测转化生长因子-β(TGF-β)和碱性成纤维细胞生长因子(bFGF)在儿童原发性局灶节段性肾小球硬化(FSGS)肾组织中的表达情况,并分析其与肾小管间质病理变化的关系,以了解TGF-β与bFGF在原发性FSGS发生发展中的作用。方法:选择肾活检明确诊断为原发性FSGS患儿的肾组织共43例,其中不伴有肾小管间质病变的FSGS肾组织共16例,设为实验1组;伴有肾小管间质病变的FSGS肾组织共27例,为实验2组。另将同期因孤立性血尿入院肾活检证实为非FSGS、病理改变较轻的肾组织作为对照组,共17例。采用免疫组化法检测细胞/生长因子TGF-β、bFGF在各组中的表达。通过方差分析(ANOVA)和相关分析法分析细胞/生长因子的表达与FSGS肾组织病理变化的关系以及细胞/生长因子之间的相互作用关系。结果:TGF-β、bFGF在各组肾组织中均有表达,表达量在对照组、实验1组和实验2组中依次升高,各组间的差异均具有统计学意义(P〈0.05);且TGF-β和bFGF的表达与肾小管间质指数呈正相关,相关系数依次为0.763和0.661。此外,TGF-β和bFGF两者的表达量经相关分析也显示呈正相关,相关系数为0.587。结论:TGF-β和bFGF在原发性FSGS患儿肾组织中高表达;随着FSGS的发展,它们在肾组织中表达量不断增加,促使肾小管间质向纤维化发展,而且两者在促进肾脏纤维化具有一定的协同作用。 相似文献
23.
目的 观察免疫抑制剂环孢素A(CsA)对大鼠肾脏成纤维细胞增殖及细胞因子表达的影响以及氟伐他汀的干预作用,探讨氟伐他汀对CsA肾毒性的保护作用。 方法 体外培养大鼠肾脏成纤维细胞,四甲基偶氮唑盐(MTT)比色法测定CsA及氟伐他汀对细胞增殖的影响。RT-PCR方法检测转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)及c-fos mRNA水平。Western印迹检测纤连蛋白(FN)的表达。 结果 CsA可明显抑制成纤维细胞增殖,且呈剂量和时间依赖效应(P < 0.05)。氟伐他汀与CsA合用后,对细胞增殖有明显的抑制作用(P < 0.01)。CsA刺激成纤维细胞TGF-β1、CTGF、c-fos及FN的产生(P < 0.05),氟伐他汀可下调这些改变(P < 0.05)。 结论 氟伐他汀可减轻CsA所致的大鼠肾脏成纤维细胞毒性 相似文献
24.
目的探讨弥漫性大B细胞淋巴瘤(DLBCL)组织中CD40L表达与DLBCL预后间的关系及意义。方法免疫组织化学法检测27例弥漫性大B细胞淋巴瘤、20例淋巴结反应性增生组织中CD40L的表达。结果(1)DLBCL中CD40L过度阳性率(25.93%)显著低于淋巴结反应性增生(63.64%),P〈0.05。(2)CD40L在Ⅲ、Ⅳ期DLBCL过度阳性率(14.29%)低于Ⅰ、Ⅱ期(38.46%),P〈0.05。CD40L过度阳性率在有结外浸润DLBCL(11.76%)低于无有结外浸润DLBCL(40%),P〈0.05。(3)DLBCL患者CD40L的过度阳性率与远处转移、临床分期均显著相关,P〈0.05。结论(1)CD40L过度阳性率与结外器官浸润及临床分期密切相关,其可能作为判断DLBCL侵袭性及预后的指标。(2)DLBCL中CD40L表达的减少可能是影响其发病的因素之一。 相似文献
25.
26.
盐酸氯胺酮-β-环糊精包合物的研究 总被引:4,自引:1,他引:3
采用正交设计法对饱和水溶液法制备盐酸氯胺酮-β-环糊精包合物的温度、时间及投料比进行选优,显微观察包合物形态,UV和X-射线衍射法测试包合物晶形变化,品尝包合物味觉效果,并测定其稳定性及溶出度。结果表明,按1:2主客克分子比,于25℃电动搅拌3h,制备包合物的包合率和收率较高,包合物已形成一种新物相,具有稳定性高,无苦味及缓释性能。 相似文献
27.
肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制 《首都医科大学学报》2023,44(1):54-61
目的 探讨肢体远隔缺血期适应(per-conditioning,PerC)联合后适应(post-conditioning,PostC)对缺血性脑卒中后神经再生的作用,并明确PerC联合PostC对脂肪酸β-氧化(fatty acid β-oxidation,FAO)限速酶——肉毒碱棕榈酰转移酶(carnitine palmitoyl transferase 1A,CPT1A)的影响。方法 对成年雄性SD大鼠进行大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)造模,MCAO模型后30 min进行肢体远隔缺血期适应治疗(PerC),再灌注24 h后重复进行肢体远隔缺血适应(PostC),1次/d,直到取材。再灌注14 d后对大鼠进行神经功能评分,通过免疫组织化学染色检测室管膜下区(subependymal ventricular zone, SVZ)神经再生情况,通过酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测CPT1A的表达。结果 与MCAO组及PerC/PostC组比较,PerC+PostC组大鼠,身体不对称运动行为评分降低,神经干细胞的数量以及向梗死区迁移的细胞数量增加。Pearson相关性分析显示,神经干细胞的数量与神经功能呈负相关(r=-0.917 9, P<0.0001)。然而,迁移到基底节区的神经干细胞的凋亡数量在各组之间差异无统计学意义。机制研究显示,PerC+PostC组CPT1A的蛋白水平显著增加。结论 PerC联合PostC治疗能够通过增加神经干细胞的数量改善神经功能,神经干细胞的脂肪酸氧化可能是其促进神经干细胞迁移的机制之一。 相似文献
28.
Class I molecules of the major histocompatibility complex bind peptides derived from cytosolic proteins and display them on the cell surface. This function alerts cytotoxic T cells to the presence of intracellular pathogens. Class I molecule assembly requires the association of the heavy chain with β2-microglobulin, accompanied by peptide loading via specific transporters. This study localizes where these assembly steps take place, using monoclonal antibodies recognizing class I molecules in different assembly states to analyze subcellular fractions of the early secretory pathway. The distribution of peptide-loaded class I molecules was more localized than the distribution of the total pool of class I molecules in the early secretory pathway. Loaded molecules colocalized with the peptide transporter, free heavy chains, and the chaperone calnexin in high density rough endoplasmic reticulum (RER) membranes. These data suggest that subunit assembly and peptide acquisition occur at the same intracellular site. Class I molecules also localized to less dense subfractions of the early secretory pathway, which contained comparatively less peptide-loaded molecules than the high density RER fractions, at steady state. Following a 15 °C temperature block, class I molecules accumulated in these less dense membrane fractions, indicating that these fractions represent the intermediate compartment where empty class I molecules are trapped in mutant cells. In the presence of cycloheximide, a pool of class I molecules recycling to the RER was detected, suggesting empty molecules recycle to acquire peptide. 相似文献
29.
Mannose binding lectin and C3 act as recognition molecules for infectious agents in the vagina 总被引:8,自引:0,他引:8
Pellis V De Seta F Crovella S Bossi F Bulla R Guaschino S Radillo O Garred P Tedesco F 《Clinical and experimental immunology》2005,139(1):120-126
In our study we examined the early complement components in patients with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and in healthy controls. The levels of C1q, mannose-binding lectin (MBL) and C3 were measured by ELISA in the cervicovaginal lavage (CVL) from gynaecological patients and controls. No significant differences were observed in the levels of these proteins in the three study groups. Immunofluorescence analysis of the clue cells and Candida hyphae from BV and VVC patients for surface-bound complement components showed the presence of C3, while C1q was undetectable. MBL was revealed on clue cells but not on Candida. Binding of MBL to Candida, grown or cytocentrifuged from the CVL of VVC patients, was found to be pH dependent and occurred between pH 4.5 and pH 5.5. In conclusion, we demonstrated that MBL and C3 present in the vaginal cavity act as recognition molecules for infectious agents that colonize the cervicovaginal mucosa. Our finding that MBL, but not C1q, binds to bacteria and fungi in vagina suggests that the lectin and classical pathways of complement activation may play a different role in immune defence in the female genital tract. 相似文献
30.
Seelen MA Trouw LA van der Hoorn JW Fallaux-van den Houten FC Huizinga TW Daha MR Roos A 《Clinical and experimental immunology》2003,134(2):335-343
In systemic lupus erythematosus (SLE), autoantibodies directed against complement components of the classical pathway, especially against C1q, are associated with severe disease and are of prognostic value for flares of lupus nephritis. Mannose-binding lectin (MBL), the recognition unit of the MBL pathway of complement activation, has structural similarities to C1q. Deficiencies of MBL have been shown to predispose to the development of SLE and to influence the course of the disease. We hypothesized that the presence of autoantibodies to MBL, analogous to autoantibodies to C1q in patients with SLE, may contribute to disease development. The occurrence of anti-MBL autoantibodies was assessed by enzyme-linked immunosorbent assay (ELISA) of 68 serum samples from 20 patients with SLE and in serum from 70 healthy controls. Levels of antibodies directed against MBL were significantly higher in patients with SLE compared to healthy subjects. No significant difference was found between patients with active disease compared to those with inactive disease. While the occurrence of anti-C1q autoantibodies was associated with renal involvement, no such relationship was found for anti-MBL autoantibodies. A significant correlation was found between anti-MBL and anti-C1q antibody levels. The level of anti-MBL antibodies was negatively correlated with MBL-complex activity of circulating MBL. Anti-MBL autoantibodies were of the immunoglobulin G (IgG) isotype and the binding site of IgG anti-MBL was located in the F(ab')2 portion. We conclude that anti-MBL are present in sera from SLE patients and influence the functional activity of MBL. 相似文献