全文获取类型
收费全文 | 152544篇 |
免费 | 11535篇 |
国内免费 | 6274篇 |
专业分类
耳鼻咽喉 | 766篇 |
儿科学 | 3036篇 |
妇产科学 | 1711篇 |
基础医学 | 23483篇 |
口腔科学 | 2552篇 |
临床医学 | 12083篇 |
内科学 | 25584篇 |
皮肤病学 | 2365篇 |
神经病学 | 13399篇 |
特种医学 | 2347篇 |
外国民族医学 | 32篇 |
外科学 | 10069篇 |
综合类 | 21411篇 |
现状与发展 | 35篇 |
预防医学 | 9594篇 |
眼科学 | 2098篇 |
药学 | 22476篇 |
21篇 | |
中国医学 | 5804篇 |
肿瘤学 | 11487篇 |
出版年
2024年 | 278篇 |
2023年 | 1818篇 |
2022年 | 3847篇 |
2021年 | 5245篇 |
2020年 | 4483篇 |
2019年 | 4740篇 |
2018年 | 4670篇 |
2017年 | 4656篇 |
2016年 | 4971篇 |
2015年 | 5633篇 |
2014年 | 8975篇 |
2013年 | 10624篇 |
2012年 | 9328篇 |
2011年 | 10649篇 |
2010年 | 8683篇 |
2009年 | 7993篇 |
2008年 | 8044篇 |
2007年 | 7613篇 |
2006年 | 6763篇 |
2005年 | 6151篇 |
2004年 | 5210篇 |
2003年 | 4550篇 |
2002年 | 3590篇 |
2001年 | 3097篇 |
2000年 | 2569篇 |
1999年 | 2323篇 |
1998年 | 2085篇 |
1997年 | 1882篇 |
1996年 | 1579篇 |
1995年 | 1346篇 |
1994年 | 1247篇 |
1993年 | 1077篇 |
1992年 | 931篇 |
1991年 | 874篇 |
1990年 | 754篇 |
1989年 | 613篇 |
1988年 | 585篇 |
1987年 | 486篇 |
1986年 | 457篇 |
1985年 | 1209篇 |
1984年 | 1392篇 |
1983年 | 1046篇 |
1982年 | 1190篇 |
1981年 | 1100篇 |
1980年 | 844篇 |
1979年 | 733篇 |
1978年 | 546篇 |
1977年 | 441篇 |
1976年 | 486篇 |
1975年 | 374篇 |
排序方式: 共有10000条查询结果,搜索用时 218 毫秒
201.
David S. Park Paul Manowitz Stanley Stein Ronald D. Poretz 《Alcoholism, clinical and experimental research》1996,20(2):234-239
Several electrophoretic forms of human platelet arylsulfatase A (ASA), including variant type IIIa and normal type IVa , have been identified by nondenaturing polyacrylamide gel electrophoresis. An alcoholic population that we have analyzed is enriched in variant type IIIa compared with nonalcoholic psychiatric and normal controls. Individuals with the IIIa enzyme possess greatly reduced levels of ASA activity. To understand further the structural basis for the differences and their potential biological consequences, the nature of the ASA variant expressed by fibroblasts from different individuals was explored. The electrophoretic patterns of fibroblast ASA from the IIIa and IVa individuals differ in degree of phosphorylation. Furthermore, fibroblast ASA from IIIa individuals lacks an N -linked glycan found in ASA from IVa individuals. In addition, differences in peptide and/or posttranslational modification unrelated to the N -linked carbohydrate or phosphorylation exist between the fibroblast ASA from IIIa and IVa individuals. The finding that both fibroblasts and platelets exhibit related electrophoretic isoform patterns characteristic of the donor's ASA type allows for the use of fibroblasts to study the impact of ethanol on the metabolism of cells possessing different ASA types. 相似文献
202.
Dr. S. Eggstein MD G. Manthey MT T. Hirsch PhD F. Baas MA B. U. V. Specht MD E. H. Farthmann MD 《Digestive diseases and sciences》1996,41(6):1069-1075
Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr). 相似文献
203.
周围神经65KD蛋白单克隆抗体的制备 总被引:1,自引:0,他引:1
神经化学诱向生长的研究是神经科学中的一个重要方向。本文以自然系统聚丙酰胺凝胶电泳,分离提取坐骨神经损伤后的远侧端中具有诱神经生长作用的65KD蛋白。以该蛋白作为抗原免疫BALB/C小鼠,通过杂交瘤技术获得一株(VI5E)稳定分泌单克隆抗体的杂交瘤细胞株。免疫印迹法表明,该单克隆抗体特异性地与65KD区带结合。免疫组化法显示,在损伤后的坐骨神经远侧端组织中的雪旺氏细胞呈阳性反应。单克隆抗体的制备为进一步阐明该蛋白的生物学特性奠定了基础。 相似文献
204.
应用标准微电极技术,研究了关附甲素对豚鼠右心室乳头肌动作电位最大除极速率(Vmax)的频率依赖性抑制作用(RDB),并与美西律,奎尼丁,劳卡尼进行了比较. 在相同刺激间隔(300 ms),产生50%左右RDB的药物浓度下,美西律的RDB开始最快,其第2个Vmax所产生的抑制已占RDB的64%,奎尼丁,劳卡尼和关附甲素的RDB开始速率常数分别为每个动作电位0.165, 0.076和0.136. 美西律,奎尼丁,劳卡尼和关附甲素产生RDB的恢复时间常数分别为1.4, 9.0, 18.2和44.0 s,而且它们的恢复时间常数是不依赖于药物浓度而变化的,结果提示,关附甲素是一个慢动力学钠通道阻滞剂. 相似文献
205.
肿瘤转移相关蛋白在甲状腺乳头状腺癌伴淋巴结转移组织中的原位表达研究 总被引:1,自引:0,他引:1
利用免疫组化ABC法,研究甲状腺乳头状腺癌,甲状腺腺瘤和正常甲状腺组织中的肿瘤转移相关基因蛋白CD44v6,EGFR,转移抑制基因nm23-H1和抑癌基因p53蛋白的原位表达。结果发现CD44v6和EGFR表达上调与肿瘤转移密切相关(P<0.05,P<0.01),而nm23-H1的表达与肿瘤转移抑制密切相关(P<0.01)。这提示肿瘤转移相关基因和转移抑制基因之间的表达失衡是甲状腺乳头状腺癌易发生转移的重要原因。 相似文献
206.
K. Arima Minako Nakamura Nobuhiko Sunohara Masafumi Ogawa Midori Anno Yoko Izumiyama Shigeo Hirai Kazuhiko Ikeda 《Acta neuropathologica》1997,93(6):558-566
Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive
supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This
report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five
PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were
the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules
were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the
inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised,
at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation
of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia
of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there
are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.
Received: 4 October 1996 / Accepted: 6 December 1996 相似文献
207.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
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
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
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
208.
作者用免疫组化ABC法对41例胆囊癌标本核苷二磷酸激酶(NDPK,下同)/nm23表达进行了测定,结果发现:nm23在恶性肿瘤中的表达率明显高于良性病变(P<0.05)。NDPK/nm23表达与胆囊癌组织的分化、局部浸润及淋巴转移密切相关(P<0.01)。NDPK/nm23阳性患者生存中位数12.25个月,阴性患者6.5个月,两者存在显著差异(P<0.01),提示nm23检测对预后有重要价值。 相似文献
209.
本实验研究切除卵巢造成肾虚骨质疏松症大鼠模型。通过观测红细胞膜蛋白激酶C(PKC)和Ca2+-Mg2_-ATP酶的活性,探讨肾虎骨质疏松症病理机制中肌醇脂质系统的变化,并结合全身和脊柱骨密度(BMD)指标观察了补肾中药(密骨灵)的疗效,与正常对照组、模型空白组和阳性药(骨疏康颗粒剂)对照组进行对照,探讨补肾法的防治机理。结果表明;模型空白组大鼠红细胞膜PKC和Ca2+-Mg2+-ATP酶、Mg2+-ATP酶的活性明显低于正常组(p均<0.05);密骨灵组与骨疏康组大鼠全身、脊柱BMD和红细胞膜PKC、Ca2+-Mg2+-ATP酶的活性均明显高于模型空白组(p均<0.05),并且与正常组大鼠无明显差别(p均>0.05);密骨灵组大鼠红细胞膜Mg2+-ATP酶活性高于模型空白组和骨疏康组(p<0.05),并且与正常组无显著性差异(p>0.05);密骨灵组大鼠红细胞膜PKC活性高于骨疏康组(P<0.05)。结论:肾虎骨质疏松症具有红细胞膜PKC和Ca2+-Mg2+-ATP酶、Mg2+-ATP酶活性的改变;密骨灵可以恢复肾虎骨质疏松症大鼠全身骨量,达到防治目的;补肾中药可以恢复红细胞膜PKC活性和钙镁泵的活性,是补 相似文献
210.
The effect of Cyclosporin A (CsA) on prostaglandin E2 (PGE2 ) production in human gingival fibroblasts challenged with tumor necrosis factor alpha (TNF-α) was studied. TNF-α (1-100 ng/ml) dose-dependently stimulated PGE2 ; formation in 24 h cultures. CsA (1-100 ng/ml) did not induce PGE2 ; formation itself but potentiated TNF-α induced PGE; formation in gingival fibroblasts in a manner dependent on the concentrations of both CsA and TNF-α. TNF-α (10 ng/ml) stimulated the release of [3 H]-arachidonic acid (A.A) from prelabelled fibroblasts that was potentiated by CsA (100 ng/ml). Addition of exogenous unlabelled AA (5-20 μM/ml) to the cells resulted in enhanced PGE2 : formation that was not potentiated by CsA (100 ng/mi). Furthermore. CsA (100 ng/ml) did not further increase the level of cyclooxygenase-2 mRNA induced by TNF-α (10 ng/ml). although PGE2 formation was enhanced. The results indicate that CsA and TNF-α act in concert on PGE2 formation in gingival fibroblasts. which may be of importance in the pathogenesis of gingival overgrowth induced by the drug. 相似文献