全文获取类型
收费全文 | 46714篇 |
免费 | 3337篇 |
国内免费 | 190篇 |
专业分类
耳鼻咽喉 | 375篇 |
儿科学 | 1506篇 |
妇产科学 | 1200篇 |
基础医学 | 6587篇 |
口腔科学 | 590篇 |
临床医学 | 5032篇 |
内科学 | 9732篇 |
皮肤病学 | 876篇 |
神经病学 | 5542篇 |
特种医学 | 1121篇 |
外科学 | 4155篇 |
综合类 | 381篇 |
一般理论 | 58篇 |
预防医学 | 5665篇 |
眼科学 | 618篇 |
药学 | 2974篇 |
中国医学 | 86篇 |
肿瘤学 | 3743篇 |
出版年
2024年 | 59篇 |
2023年 | 651篇 |
2022年 | 1087篇 |
2021年 | 2145篇 |
2020年 | 1298篇 |
2019年 | 1772篇 |
2018年 | 2034篇 |
2017年 | 1361篇 |
2016年 | 1515篇 |
2015年 | 1659篇 |
2014年 | 2024篇 |
2013年 | 2621篇 |
2012年 | 4195篇 |
2011年 | 4149篇 |
2010年 | 2103篇 |
2009年 | 1844篇 |
2008年 | 2944篇 |
2007年 | 2906篇 |
2006年 | 2775篇 |
2005年 | 2569篇 |
2004年 | 2279篇 |
2003年 | 2034篇 |
2002年 | 1731篇 |
2001年 | 193篇 |
2000年 | 142篇 |
1999年 | 207篇 |
1998年 | 347篇 |
1997年 | 261篇 |
1996年 | 212篇 |
1995年 | 176篇 |
1994年 | 123篇 |
1993年 | 117篇 |
1992年 | 68篇 |
1991年 | 65篇 |
1990年 | 55篇 |
1989年 | 59篇 |
1988年 | 49篇 |
1987年 | 37篇 |
1986年 | 39篇 |
1985年 | 35篇 |
1984年 | 46篇 |
1983年 | 44篇 |
1982年 | 33篇 |
1981年 | 41篇 |
1980年 | 28篇 |
1979年 | 17篇 |
1978年 | 13篇 |
1977年 | 20篇 |
1975年 | 9篇 |
1973年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
31.
Laura Cisneros Maria-Carlota Londo?o Carmen Blasco Ramón Bataller Rosa Miquel Miquel Bruguera Pere Ginès Antoni Rimola 《Liver transplantation》2007,13(7):1017-1027
The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered. 相似文献
32.
Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro. 总被引:1,自引:0,他引:1
Rosemary Masterson Tim D Hewitson Kristen Kelynack Marina Martic Laura Parry Ross Bathgate Ian Darby Gavin Becker 《Nephrology, dialysis, transplantation》2004,19(3):544-552
BACKGROUND: Renal fibroblasts are important effector cells in tubulointerstitial fibrosis, with experimental antifibrotic strategies focusing on the functional down-regulation of these cells. Several experimental models of fibrosis have provided evidence for the effectiveness of the polypeptide hormone relaxin as a potential antifibrotic agent. This study was conducted to further elucidate the antifibrotic mechanisms of relaxin on renal fibroblasts in vitro. METHODS: Rat cortical fibroblasts were obtained from outgrowth culture of renal tissue isolated from kidneys 3 days post-unilateral ureteric obstruction and constituted 100% of cells studied. A relaxin radio-receptor assay was used to establish binding of relaxin to renal fibroblasts in vitro. Functional studies then examined the effects of H2 relaxin (0, 1, 10 and 100 ng/ml) on fibroblast kinetics, expression of alpha-smooth muscle actin (alpha-SMA), total collagen synthesis, collagenase production and collagen-I lattice contraction. CTGF mRNA expression was also measured by northern analysis. RESULTS: H2 relaxin bound with high affinity to rat renal fibroblasts, but receptor numbers were low. Consistent with its previously reported bimodal effect, transforming growth factor (TGF-beta 1) reduced fibroblast proliferation, an effect abrogated by H2 relaxin. Fibroblasts exposed to H2 relaxin (100 ng/ml) for 24 h demonstrated decreased immunostaining for alpha-SMA and reduced alpha-SMA protein expression compared with controls. There was a trend for a relaxin-mediated reduction in total collagen synthesis and alpha 1(I) mRNA expression with large dose-related increases in collagenase protein expression being observed. TGF-beta 1-stimulated collagen-I lattice contraction was significantly inhibited following co-incubation with 100 ng/ml relaxin. Incremental doses of H2 relaxin had no significant effect on CTGF mRNA expression. CONCLUSIONS: The findings of this study suggest that the antifibrotic effects of relaxin involve down-regulation of fibroblast activity, increase in collagenase synthesis and restructuring of collagen-I lattices, which are consistent with its known physiological role of matrix remodelling. Although there appears to be an interaction between TGF-beta 1 and H2 relaxin, this does not appear to involve a reduction in CTGF mRNA expression. 相似文献
33.
34.
35.
36.
Floriano P Silva-Junior Herbert L M Guedes Laura C Garvey Aniesse S Aguiar Saulo C Bourguignon Enrico Di Cera Salvatore Giovanni-De-Simone 《Toxicon》2007,50(1):18-31
BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da by electron spray mass spectrometry. The enzyme was shown to be highly glycosylated with 42% of N-linked carbohydrates composed of Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6-aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective. The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin-like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1muM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like protein C, protease-activated receptor-1 or inhibitors such as hirudin and antithrombin. A non-denaturing procedure using PNGase F and neuraminidase followed by hydrophobic interaction chromatography was employed to obtain active BJ-48 forms with variable carbohydrate content. Compared to the native enzyme, total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in their specific activities upon heating at 55/65 degrees C or treatment with SBTI. These results point out a role for BJ-48 glycosylation in thermostability and controlling the access of some canonical protein inhibitors to the active site. 相似文献
37.
Mice homozygous for the lpr mutation have B and T cell defects and develop autoantibodies, suggesting that lpr plays a role in their genesis. The lpr defect has been identified as a mutation in the apoptosis-associated Fas receptor (FasR) gene. To begin to define the role of FasR in B cells, we have surveyed FasR expression on B-lineage cells from early progenitors in the bone marrow through their maturation in the periphery. Contrary to some reports, we found that FasR is expressed on B cells at all stages of their development and is highest on germinal center B cells. FasR is not expressed on lpr/lpr-derived cells. These data are consistent with the idea that lpr/lpr mice have an intrinsic B cell defect that may be manifested in developing as well as peripheral B cells. An unexpected finding is that B-1 (CD5) B cells do not constitutively express FasR: FasR becomes detectable on B-1 B cells only after activation. 相似文献
38.
Franco Rilke M. D. F. R. C. Umberto Veronesi M. D. Alberto Luini M. D. Cristina Brambilla M. D. Viviana Galimberti M. D. Stefano Zurrida M. D. Silvana Pilotti M. D. M. I. A. C. Silvana Di Palma M. D. Roberto Zucali M. D. Laura Lozza M. D. 《The breast journal》1996,2(3):176-180
Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored. 相似文献
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored. 相似文献
39.
R. Christopher Pierce Amy J. Clemens Laura A. Shapiro George V. Rebec 《Psychopharmacology》1994,116(1):103-109
Acute administration of neuroleptic drugs alters the extracellular level of ascorbate in the neostriatum, and increasing evidence suggests a role for this vitamin in the behavioral, and possibly therapeutic, effects of these drugs. To shed further light on this issue, extracellular ascorbate was recorded in the neostriatum and nucleus accumbens of awake, behaving rats following chronic treatment with either classical (haloperidol) or atypical (clozapine) neuroleptics or ascorbate itself. Electrochemically modified, carbon-fiber microelectrodes were lowered in place the day after the last of 21 daily injections of either haloperidol (0.5 mg/kg, SC), clozapine (20 mg/kg, IP), sodium ascorbate (500 mg/kg, IP) or vehicle. Voltammetric measurements were obtained during quiet rest and following administration ofd-amphetamine (2.5 mg/kg). Repeated treatment with either haloperidol or ascorbate elevated basal extracellular ascorbate and potentiated the amphetamine-induced increase in ascorbate release in neostriatum but not nucleus accumbens. Both treatment groups also showed a significant increase in amphetamine-induced sniffing and repetitive head movements compared to vehicle-treated animals. In contrast, repeated clozapine had no effect on extracellular ascorbate in either neostriatum or nucleus accumbens, but increased the locomotor response to an amphetamine challenge. Thus, to the extent that increases in neostriatal ascorbate exert neuroleptic-like effects, such effects are likely to parallel haloperidol rather than clozapine. 相似文献
40.