全文获取类型
收费全文 | 1100篇 |
免费 | 53篇 |
国内免费 | 37篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 10篇 |
妇产科学 | 3篇 |
基础医学 | 70篇 |
口腔科学 | 10篇 |
临床医学 | 146篇 |
内科学 | 161篇 |
皮肤病学 | 6篇 |
神经病学 | 95篇 |
特种医学 | 44篇 |
外科学 | 64篇 |
综合类 | 292篇 |
预防医学 | 21篇 |
眼科学 | 11篇 |
药学 | 142篇 |
中国医学 | 18篇 |
肿瘤学 | 96篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 18篇 |
2020年 | 18篇 |
2019年 | 13篇 |
2018年 | 14篇 |
2017年 | 13篇 |
2016年 | 24篇 |
2015年 | 21篇 |
2014年 | 46篇 |
2013年 | 50篇 |
2012年 | 42篇 |
2011年 | 52篇 |
2010年 | 47篇 |
2009年 | 39篇 |
2008年 | 44篇 |
2007年 | 55篇 |
2006年 | 49篇 |
2005年 | 73篇 |
2004年 | 53篇 |
2003年 | 55篇 |
2002年 | 58篇 |
2001年 | 49篇 |
2000年 | 50篇 |
1999年 | 52篇 |
1998年 | 35篇 |
1997年 | 22篇 |
1996年 | 28篇 |
1995年 | 33篇 |
1994年 | 15篇 |
1993年 | 13篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 10篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1973年 | 2篇 |
排序方式: 共有1190条查询结果,搜索用时 125 毫秒
1.
刘素艳 《中华综合医学杂志(哈尔滨)》2005,6(3):204-205
目的:探讨尿激酶与急性脑梗死(ACI)患者特异性烯醇化酶(NSE)的关系。方法:该实验采用酶联免疫吸附法(EusA)测定脑梗死常规治疗组、尿激酶治疗组血清NSE水平。结果:尿激酶组NSE值显著低于ACI常规治疗组。结论:尿激酶能降低血清酶活性,使已形成的纤维蛋白水解,从而缩小梗死灶体积,改善脑缺血、缺氧,从而起到保护脑细胞的作用。 相似文献
2.
BACKGROUND: As a non-invasive technique which can provide comprehensive biological information, 1H-magnetic resonance spectroscopy (1H-MRS) may provide valuable reference data for irreversible recovery or reversible changes in ischemic tissue after stroke.
OBJECTIVE: To monitor and evaluate the effect of the urokinase thrombolytic therapy after experimental acute cerebral ischemia by 1H-MRS technology and investigate its adaptability.
DESIGN: Randomly controlled animal study.
SETTINGS: Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science.
MATERIALS: Eleven healthy adult Sprague-Dawley (SD) rats, weighing 260–300 g and of both genders, were supplied by Experimental Animal Center of Tongji Medical Collage, Huazhong University of Science and Technology [SCXK (e) 2004-007]. 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company.
METHODS: The experiment was carried out in Shenzhen Hospital of Peking University and National Key Laboratory of Pattern and Atom & Molecular Physics, Wuhan Physics and Mathematics Institute, Chinese Academy of Science from August 2003 to December 2005. ① The rats were randomly divided into 30-minute self-thrombo-embolism group (n =6) and 60-minute self-thrombo-embolism group (n =5). Six rats in 30-minute self-thrombo-embolism group were occluded with clot embolus for 30 minutes and 5 rats in 60-minute self-thrombo-embolism group were occluded for 60 minutes. 10 000 U/kg urokinase was dissolved in 2 mL saline and the operation lasted for 5 minutes. ② 1H-MRS was performed before thrombolysis and at 3 hours and 24 hours after successful embolization. The metabolic changes of N-acetyl-L-aspartic acid (NAA)/phosphocreatine (PCr) + creatine (Cr), choline phosphate (Cho)/PCr+Cr and lactic acid (Lac)/PCr+Cr in the region of interests were analyzed. ③ The T2W image was conducted 24 hours after the thrombolytic therapy with TR=500 ms and TE=25 ms. ④ The subjects were sacrificed immediately after 1H-MRS and the brain tissues were cut into pieces and stained with HE method; in addition, pathological changes were observed under optic microscope.
MAIN OUTCOME MEASURES: ① Metabolic changes of NAA/PCr+Cr, Cho/PCr+Cr and Lac/PCr+Cr in the region of interests; ② T2W image at 24 hours after the thrombolysis; ③ pathological observation of brain tissue.
RESULTS: Eleven rats were all involved in the final analysis. ① Metabolic changes in the region of interests : In 30-minute self-thrombo-embolism group, the Lac peak emerged immediately after the embolism, but the ischemic zone decreased 3 hours after the thrombolytic therapy (0.252±0.01, 0.603±0.01, P < 0.01). Lac/(PCr+Cr) ratio was 0.290±0.01 at 24 hours after thrombolysis, which was higher than that at 3 hours after thrombolysis (P < 0.01). The NAA/ (PCr+Cr) ratio decreased significantly at 3 hours after the thrombolysis as compared with that before thrombolysis (0.922±0.16, 1.196±0.01, P < 0.05). In 60-minute self-thrombo-embolism group, the Lac/(PCr+Cr) ratio was higher at 3 hours after thrombolysis than that before thrombolysis (0.846±0.12, 0.601±0.11, P < 0.05) and the NAA/(PCr+Cr) decreased at 3 hours after the embolism. Fluctuation of NAA/ (PCr+Cr) ranged from 0.68 to 0.75 before thrombolysis and from 0.71 to 0.75 at 3 hours after thrombolysis. ② T2W image: T2W image showed that 2 subjects in 30-minute self-thrombo-embolism group whose Lac/NAA was higher than 0.7 suffered from intracranial hemorrhage. This meant that the subjects with Lac/NAA > 0.7 were more likely to suffer from intracranial hemorrhage. ③ Histological and morphological examinations: Optic microscope demonstrated that interspace surrounding nerve cells was widened at ischemic center; neurons were swelling; nucleus was stained lightly; pyknosis and mesenchymal edema were mainly observed in lateral cortex of brow and vertex and in lateral part of corpus striatum.
CONCLUSION: ①Compound parameters in ischemic area before thrombolysis should be regarded as an important predicting marker for thrombolytic therapy, effect evaluation and termination. ② 1H-MRS combining with other imaging technique is a detecting way for screening cases who are suitable for thrombolytic therapy. 相似文献
3.
目的尝试用小剂量尿激酶治疗老年高龄急性心肌梗死,旨在使老年高龄患者亦从溶栓治疗中获益.方法采用WHO关于急性心肌梗死(AMI)的诊断标准,收治老年高龄患者65例.随机分为两组,溶栓组31例,给予小剂量尿激酶(50×104U)30min 静脉滴入;并与非溶栓组34例对照观察.结果溶栓组冠脉再通率、五周病死率、休克、心衰分别为54.8%、6.4%、3.2%、9.7%;而对照组分别为14.7%、23.5%、26.5%:41.2%,有明显差异(P<0.01).结论有条件的基层医院依然有可能实施小剂量尿激酶对老年高龄患者的溶栓治疗,且可挽救更多老年高龄患者的生命. 相似文献
4.
提纯出受损伤内皮细胞的特异性抗原,再用免疫学方法制得相应抗体,并把它与尿激酶形成结合物。在人工造成血管内皮细胞损伤的动物中,分别用尿激酶结合物、单纯特异性抗体处理,各组动物处死后进行形态学观察。结果显示:在未用尿激酶结合物处理的动物血管内和使用结合物处理的血管内,血栓形成的程度有明显的差别,前者明显,后者轻微。这种方法既能预防血栓形成,又不会产生继发性出血的危险。 相似文献
5.
WANGXiang-tao HOUXin-pu 《中国药学》2003,12(3):171-172
Becauseofvariousthrombolyticagentsnowavailableassociatedwithlowthrombolyticspecificity ,largedoserequiredforclinicaltreatment,andperplexingsideeffectofhemorrhage ,westudiedthethrombus targetedliposomeswhichhavespecificaffinitytoactivatedplatelets .WithtetrapeptideRGDSasthehomingdevice ,theobtainedliposomescanspecifi callyrecognizethereceptorGPIIb IIIaoftheactivatedplateletsinthrombus ,bywhichthrombustargetabilityisachieved .Thefollowingpartsareincludedinthestudy .Eggphosphatidylcholine (E… 相似文献
6.
7.
Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis 总被引:3,自引:0,他引:3
Increased expression of the hepatocyte growth factor (HGF) receptor (c-met) and urokinase type plasminogen (uPA) correlated
with the development and metastasis of cancers. To investigate the role of HGF/c-met signaling on metastasis in cancer cells
stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580)
on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2. Pretreatment of PD98059 decreased HGF-mediated
phosphorylation of extracellular receptor kinase (ERK), uPA secretion and expression of matrix metalloproteinases (MMP-2 and
MMP-9) in a dose-dependent manner. In contrast, SB203580 pretreatment increased HGF-stimulated ERK phosphorylation, uPA secretion
and expression of MMPs. SB203580 also reversed the inhibition of HGF-mediated ERK activation and uPA secretion in the PD98059-pretreated
cells. These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer
and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
8.
Brooks TD Slomp J Quax PH De Bart AC Spencer MT Verheijen JH Charlton PA 《Clinical & experimental metastasis》2000,18(6):445-453
Recent reports suggest that elevated levels of plasminogen activator inhibitor-1 (PAI-1) may contribute to tumour progression.
The studies reported here were designed to help elucidate PAI-1's contribution to the invasive and migratory phenotype. Antibodies
to PAI-1 dose-dependently, and significantly, inhibited the invasive and migratory potential of human HT1080 fibrosarcoma
cells, as did an antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human melanoma cell line, BLM, was also
attenuated by the anti-PAI-1 monoclonal antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not express
uPA, provided further confirmation of PAI-1 and uPA's role as, upon transfection with uPA, this cell line attained an invasive
phenotype, which was again attenuated by MAI- 12. Although antibodies to PAI-1 did not affect the adhesion of HT1080 cells
to vitronectin, the antibody to uPA reduced their attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell
adhesion (IC50 180nM) and promoted cell detachment from vitronectin. Furthermore melanoma cells transfected with a uPA variant, which had
an impaired interaction with PAI-1, were not invasive and had impaired binding to vitronectin. These data highlight the importance
of a balanced proteolysis and suggest an additional role for PAI-1 distinct from its role in proteolysis. These data also
suggest that uPA and PAI-1 may co-operate in the migratory process by respectively facilitating the attachment to, and subsequent
detachment from, vitronectin in the extracellular matrix. These results support the clinical findings and indicate that modulation
of PAI-1 activity may be of therapeutic benefit for the treatment of cancer.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
9.
Qu CF Song EY Li Y Rizvi SM Raja C Smith R Morgenstern A Apostolidis C Allen BJ 《Clinical & experimental metastasis》2005,22(7):575-586
Purpose: The urokinase plasminogen activator (uPA) and its receptor (uPAR) are expressed by pancreatic cancer cells and can be targeted
by the plasminogen activator inhibitor type 2 (PAI2). We have labeled PAI2 with 213Bi to form the alpha conjugate (AC), and have studied its in vitro cytotoxicity and in vivo efficacy.
Methods and Materials: The expression of uPA/uPAR on pancreatic cell lines, human pancreatic cancer tissues, lymph node metastases, and mouse xenografts
were detected by immunohistochemistry, confocal microscopy, and flow cytometry. Cytotoxicity was assessed by the MTS and TUNEL
assay. At 2 days post-cancer cell subcutaneous inoculation, mice were injected with AC by local or systemic injection.
Results: uPA/uPAR is strongly expressed on pancreatic cancer cell lines and cancer tissues. The AC can target and kill cancer cells
in vitro in a concentration-dependent fashion. Some 90% of TUNEL positive cells were found after incubation with 1.2 MBq/ml of AC.
A single local injection of ~222 MBq/kg 2 days post-cell inoculation can completely inhibit tumor growth over 12 weeks, and
an intraperitoneal injection of 111 MBq/kg causes significant tumor growth delay.
Conclusions: 213Bi-PAI2 can specifically target pancreatic cancer cells in vitro and inhibit tumor growth in vivo. 213Bi-PAI2 may be a useful agent for the treatment of post-surgical pancreatic cancer patients with minimum residual disease. 相似文献
10.
Fox SB Taylor M Grøndahl-Hansen J Kakolyris S Gatter KC Harris AL 《The Journal of pathology》2001,195(2):236-243
The generation of urokinase plasminogen activator (uPA) by tumours is an important pathway for neoplastic cell invasion and metastasis. Indeed in several tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor plasminogen activator inhibitor-1 (PAI-1) is associated with a poorer prognosis. Since endothelial cells also use this proteolytic system to remodel the extracellular matrix during angiogenesis and since angiogenesis, as assessed by microvessel density, is also a predictor of patient survival, this study was designed to investigate the relationship between angiogenesis and the urokinase system in breast tumours. The aims were to assess whether the uPA, uPAR and/or PAI-1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis. The study also sought to examine the relationship between the uPA system and vessel remodelling using loss of a basement membrane epitope (LH39) normally associated with established capillaries. The cytosolic levels of uPA, PAI-1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay, together with tumour vascularity, in 136 well-characterized invasive breast carcinomas. There were significant relationships between uPA and uPAR (Spearman r=0.37, p<0.0001), uPA and PAI-1 (Spearman r=0.19, p=0.03) and between uPAR and PAI-1 (Spearman r=0.23 p=0.01). A significant correlation was also observed between PAI-1 and vessel remodelling (Spearman r=0.34, p=0.04), patient age (p=0.01), nodal status (p=0.047) and tumour grade (p=0.04), but no association between tumour vascularity and PAI (p=0.96), uPA (p=0.69) or uPAR (p=0.81) was present. No significant association was seen between any of the urokinase variables and expression of the angiogenic factor thymidine phosphorylase. Furthermore, no significant associations were found between any of the studied parameters and overall survival in a univariate analysis of the cancer patients. A multivariate Cox proportional hazard model of overall survival showed that uPA (p=0.15), but not uPAR (p=0.52) or PAI-1 (p=0.61), gave no additional prognostic information. These findings show that uPA may work via an independent pathway to angiogenesis and therefore combined blockade of uPA and angiogenesis may have additional therapeutic benefits. It also shows, as recently demonstrated in animal models, that PAI-1 may be a key regulator of vascular remodelling in human cancer. 相似文献