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41.
目的:探讨E26转录因子2(E-twenty six 2,Ets2)对肾癌细胞786-0迁移、侵袭的影响及其机制。方法:设计并合成特异性siRNA下调肾癌细胞系786-0中Ets2的表达;并利用划痕实验及Transwell实验检测其迁移及侵袭能力的变化;通过Western blot检测下调Ets2表达后基质金属蛋白酶2(MMP-2)及MMP-9表达水平变化。结果:siRNA能有效下调肾癌786-0细胞系中Ets2的表达。细胞划痕实验结果显示下调Ets2表达后,细胞迁移能力减弱(P<0.01);Transwell实验中NC组穿膜细胞数为(43.80±3.99)个,而siRNA1组为(23.30±4.24)个(P<0.01), siRNA2组为(24.20±3.29)个(P<0.01),细胞侵袭能力减弱。Ets2-siRNA介导的Ets2基因沉默下调了786-0细胞中MMP-2及MMP-9的表达的同时上调了基质金属蛋白酶组织抑制剂1(TIMP1)和TIMP2的表达。结论:Ets2可通过调节MMPs及TIMPs的表达影响肾癌细胞的迁移及侵袭能力。  相似文献   
42.

Introduction

The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes.

Materials and Methods

A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status). An immunohistochemical study was performed using tissue arrays and specific antibodies against MMP-9, MMP-11, and MMP-14, and TIMP-1 and TIMP-2.

Results

MMP-11 expression by MICs was significantly and strongly associated with prognosis in all breast cancer subtypes. There were other significant associations with poor prognosis in luminal A tumors: expressions of MMP-9, MMP-11, and TIMP-2 by CAFs, in luminal B tumors: MMP-14 expression by MICs and TIMP-2 expression by MICs, in HER-2-positive tumors: expression of MMP-9 by MICs, and in triple negative breast cancers: expression of TIMP-1 by MICs.

Conclusion

Characterization of both tumor stromal CAFs and MICs, with regard to the expression of MMPs and TIMPs, improve the prognostic evaluation of all breast cancer subtypes.  相似文献   
43.
目的 观察三七总皂苷(Panax notoginseng saponins,PNS)对TNF-α诱导的小鼠肾小球系膜细胞SV40 MES 13增殖及基质金属蛋白酶/基质金属蛋白酶组织抑制物(MMPs/TIMPs)表达的影响。方法 采用肿瘤坏死因子-α(Tumor Necrosis Factor,TNF-α)诱导SV40 MES 13细胞增殖,xCELLigence RTCA DP实时细胞分析系统记录120h细胞指数(CI),实时荧光定量PCR法检测96hSV40 MES 13细胞MMP-2、TIMP-2mRNA表达,ELISA法检测96hSV40 MES 13细胞上清MMP-9、TIMP-1表达。结果 PNS三个剂量组均能抑制TNF-α诱导的SV40 MES 13增殖,其中96h效果最明显;PNS高、中剂量组能提高MMP-2/ TIMP-2比值和MMP-9/ TIMP-1比值,与TNF-α组比较差异显著(P<0.05)。结论 PNS能减轻TNF-α诱导的系膜细胞增殖,其机制可能与改善MMP-2/ TIMP-2、MMP-9/ TIMP-1平衡有关。  相似文献   
44.
The histological and biochemical changes that occur in the extracellular matrix of the intervertebral disc (IVD) during ageing and degeneration have been investigated extensively. However, the mechanisms behind these changes are not fully understood. A number of studies have suggested the involvement of matrix metalloproteinases (MMPs) and ADAMTS in IVD degeneration, but few have localized the site of production of these enzymes to the cells of the degenerate disc. This study uses immunohistochemical techniques to localize and quantify the production of degrading enzymes (MMPs 1, 3, and 13, and ADAMTS 4) and their inhibitors (TIMPS 1, 2, and 3) within non-degenerate and degenerate discs of varying severity of degeneration. In all discs investigated, the cells that produced the enzymes and their inhibitors were the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus (AF), with little immunopositivity in the outer AF. Non-degenerate discs showed low numbers of cells expressing the degradative enzymes MMP 1 and ADAMTS 4, suggesting a role for these enzymes in normal homeostasis. No MMP 3 or MMP 13 immunopositivity was observed in non-degenerate discs. In degenerate discs, the number of cells immunopositive for MMPs 1, 3, 13 and ADAMTS 4 increased with the severity of degeneration. This increase in degrading enzymes was also accompanied by increases in the number of cells immunopositive for TIMPs 1 and 2 but not TIMP 3. This study highlights that although the expression of a number of MMPs increases with degeneration, this is accompanied by an increase in their inhibitors. However, the increase in the number of cells immunoreactive for ADAMTS 4 with increasing degeneration was not paralleled by a rise in its inhibitor TIMP 3. This finding indicates that the aggrecanases, rather then the MMPs, are a possible therapeutic target for the inhibition of disc degeneration.  相似文献   
45.
目的研究水飞蓟宾对NASH大鼠肝纤维化进展的影响。方法30只雄性SD大鼠随机分为正常饮食对照组(n=10)、高脂饮食模型组(n=10)和水飞蓟宾治疗组(n=10),实验时间12周。生化法检测血清AST,ALT,TG,CHO。放免法检测HA,RTPCR法检测TIMP-1、TIMP-2、MMP-2、MMP-13mRNA的表达,紫外分光光度计测量SOD及MDA。结果与模型组比较,水飞蓟宾治疗组大鼠肝功改善,HA及SOD含量下降,TIMP-1、TIMP-2、MMP-2表这降低,MMP-13及MDA升高,肝纤维化程度减轻。结论水飞蓟宾具有一定抗纤维化作用。  相似文献   
46.
基质金属蛋白酶及其抑制因子与肝纤维化   总被引:4,自引:0,他引:4  
肝纤维化是各种慢性肝病向肝硬化发展的共同病理过程,其实质是以Ⅰ、Ⅲ型胶原为主的细胞外基质(extracellular matrix,ECM)合成与降解失衡,导致ECM在肝内过度沉积。研究表明,基质金属蛋白酶类(matrix metalloproteinases,MMPs)和金属蛋白酶组织抑制因子(tissue inhibitors of metalloproteinases,TIMPs)两者的平衡在ECM的合成与降解中发挥着重要的作用。  相似文献   
47.
目的:通过大鼠断奶后极早期改变食物硬度造成的关节负荷改变,了解对颞下颌关节软骨内基质金属蛋白酶-8(MMP-8)和金属蛋白酶组织抑制因子-1(TIMP-1)表达变化的影响。方法:100只14天龄雌性大鼠同时哺乳与喂食粉末样食物,在21天龄断奶后,随机分为2组:实验组改为极硬块状食物,对照组仍然粉末样食物,食物改变后6h、12h、24h、48h以及9天分别每组各处死10只大鼠。免疫组化法了解MMP-8和TIMP-1在髁突软骨的表达和定位,并定量比较不同时间段两组间表达变化。结果:在所有时间段,MMP-8和TIMP-1主要表达在髁突软骨增殖层和软骨细胞肥大层的上层。MMP-8有时在肥大层下部的细胞外基质也有强或弱的表达。对TIMP-1和MMP-8在整个髁突软骨表达半定量分析表明:不同硬度食物组间比较,仅有MMP-8在第6h软食物组染色强度低于硬食物组(P〈0.05),其他时间段无统计差异。另一方面不同时间段比较:软食物组MMP-8表达在6h和24h、9天(P〈0.05),24h、48h和9天(P〈0.01)均有统计差异。而硬食物组在6h和12h,12h和48h(P〈0.05),6h、24h、48h和9天(P〈0.01)均有统计差异。TIMP-1软食物组表达在12h和48h,6h和24h、48h,48h和9天有统计学差异(P〈0.01);而在硬食物组,12h和48h,6、24h、48h和9天有统计学差异(P〈0.01)。结论:食物硬度改变而造成关节负荷改变,MMP-8和TIMP-1表达变化具有负荷依赖性及时间依赖性,是一种在生理范围内的,对改变负荷极早期的一种敏感、暂时、适应性的软骨代谢改变。机械负荷有可能是通过细胞外基质代谢影响髁突软骨发育的重要因素。  相似文献   
48.
目的:观察第三腰椎横突综合征模型兔横突局部肌肉组织匀浆中Ⅰ型胶原及相关代谢酶的变化,探讨针刀松解法的干预作用机制。方法:将30只日本大耳白兔随机分为正常组、模型组、针刀组、电针组和针刀+电针组5组,每组6只。后4组采用在左侧第三腰椎横突部埋置明胶海绵的方法制作第三腰椎横突综合征模型,针刀组和电针组分别给予针刀松解法和电针双侧"委中"干预,针刀+电针组则同时给予针刀松解法和电针干预。造模后第28天,取左侧第三腰椎横突周围肌肉组织,采用双抗夹心ELISA方法检测肌肉组织匀浆中Col-Ⅰ、MMP-1、MMP-2以及TIMP-1、TIMP-2含量的变化。结果:模型组肌肉组织匀浆中Col-Ⅰ、MMP-1、MMP-2较正常显著升高,TIMP-1、TIMP-2含量较正常显著降低,有显著统计学差异(P〈0.05,P〈0.01),针刀组、电针组和针刀+电针组Col-Ⅰ、MMP-1、MMP-2较模型组有上升趋势,TIMP-1、TIMP-2含量模型组有下降趋势,其中MMP-1、TIMP-1有显著统计学差异(P〈0.05)。结论:针刀松解法可调节模型动物第三腰椎横突局部肌肉组织匀浆中Col-Ⅰ、MMPs和TIMPs的合成和分泌,对ECM降解和重组之间的动态平衡起到良性的调节作用。  相似文献   
49.
C18 unsaturated fatty acids were here found to inhibit proMMP (matrix metalloproteinase)-3 activation by plasmin. This effect was suppressed by lysine ligand competitors, indicating that it was mediated by binding to kringle domains. Surface plasmon resonance analysis demonstrated that oleic acid interacted to a similar extent with plasmin and kringle 5 (KD values of 3.4 x 10(-8) and 5.9 x 10(-8)M) while interaction with kringles 1-2-3 was 10-fold lower. Furthermore, oleic acid stimulated the amidolytic activity of plasmin and mini-plasmin, but not micro-plasmin. Oleic acid also enhanced u-PA (urokinase-type plasminogen activator)-mediated plasminogen activation over 50-fold. Taken together, these data indicate that inhibition of plasmin-induced proMMP-3 activation by unsaturated fatty acids was mediated through their preferential binding to kringle 5. The influence of elaidic acid on the plasmin/MMP-3/MMP-1 proteolytic cascade was assessed ex vivo. Exogenous addition of plasmin to dermal fibroblasts or supplementation of gingival fibroblast culture medium with plasminogen triggered this cascade. In both instances, elaidic acid totally abolished proMMP-3 and proMMP-1 activation. Additionally, a significant decrease in lattice retraction and collagen degradation in a range similar to that obtained with Batimastat was observed when human gingival fibroblasts were cultured in plasminogen-containing type I collagen gels, indicative of the dual influence of unsaturated fatty acids on MMP activation and activity. In conclusion, unsaturated fatty acids or molecules with similar structures could be attractive target for the development of natural pharmacological inhibitors directed against plasmin and/or MMPs in different pathological contexts such, skin UV irradiation, vascular diseases and tumour growth and invasion.  相似文献   
50.
Tissue inhibitors of metalloproteases: Regulation and biological activities   总被引:8,自引:0,他引:8  
A central role in tissue invasion is played by proteases that degrade extracellular matrices; in particular specific metalloproteases (MMPs) have been frequently correlated with the invasive potential of tumor cells and with the angiogenic process. MMPs are tightly regulated by molecules controlling their activation and by specific inhibitors of MMPs, known as the Tissue Inhibitors of MetalloProteases or TIMPs. Four TIMP family members are currently known. An imbalance between MMPs and TIMPs is linked to the degradation of the extracellular matrix associated with several physiologic and pathologic events including angiogenesis, invasion and metastasis. TIMPs are not only the `guardians' of tissue degradation, they are able to control cell proliferation and cell survival as well. Given the critical role that TIMPs play, it is vital to know how the expression of TIMPs is controlled. Here we review the major biological properties and the molecular regulation of the TIMP expression. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
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