首页 | 官方网站   微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2202篇
  国内免费   315篇
  完全免费   20篇
医药卫生   2537篇
  2020年   1篇
  2019年   1篇
  2018年   2篇
  2017年   11篇
  2016年   26篇
  2015年   62篇
  2014年   113篇
  2013年   169篇
  2012年   253篇
  2011年   301篇
  2010年   320篇
  2009年   341篇
  2008年   363篇
  2007年   331篇
  2006年   18篇
  2005年   24篇
  2004年   19篇
  2003年   21篇
  2002年   11篇
  2001年   11篇
  1999年   25篇
  1998年   14篇
  1997年   70篇
  1996年   24篇
  1995年   6篇
排序方式: 共有2537条查询结果,搜索用时 46 毫秒
1.
Adenoviral gene therapy in gastric cancer: A review   总被引:15,自引:0,他引:15  
Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors. Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.  相似文献
2.
目的 观察黄芪注射液对缺氧缺糖后复氧复糖大鼠海马神经细胞凋亡的抑制作用.方法 取体外原代培养8 d的正常乳鼠海马神经细胞,缺氧缺糖0.5 h后正常培养,并用黄芪注射液进行干预. MTT法测定细胞活性,光学显微镜下观察细胞形态,Annexin V-FITC/PI双染法流式细胞术检测凋亡细胞百分率.结果 与正常对照组比较,缺氧缺糖后复氧复糖组(模型组)在复氧复糖后各个时间点海马神经细胞的活性明显下降(P<0.05),其中复氧复糖后6 h海马神经元活性最低,与其他时间点比较差异显著(P<0.05). 各时间点黄芪注射液低浓度组和高浓度组的细胞活性与同时间点模型组相比无显著性差异(P>0.05)黄芪注射液中浓度组各时间点的细胞活性明显增高(P<0.05).模型组各时间点细胞凋亡率较正常对照组明显升高(P<0.05),黄芪注射液组各时间点细胞凋亡率较模型组组明显下降 (P<0.05).光镜下观察模型组可见大量凋亡细胞,细胞核皱缩、碎裂,核深染并可见凋亡小体;坏死细胞肿胀,细胞膜连续性破坏;黄芪注射液组凋亡细胞明显减少且以细胞核皱缩为主,细胞坏死程度较模型组明显减轻.结论 黄芪注射液可以抑制缺氧缺糖后复氧复糖大鼠海马神经细胞的凋亡,提高细胞的活性,对缺氧缺糖后复氧复糖大鼠海马神经细胞有保护作用.  相似文献
3.
Drug-induced liver injury: Is it somehow foreseeable?   总被引:12,自引:0,他引:12  
The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.  相似文献
4.
燃煤型砷中毒患者遗传损伤及癌变机理   总被引:11,自引:11,他引:10  
目的:从遗传损害、癌基因和抑癌基因蛋白异常表达,细胞增殖和凋亡等方面对燃煤型砷中毒患者遗传损伤及癌变机理进行研究并寻找早期及灵敏的分子标记物,方法:综合应用生物化学、分子遗传学,分子病理学和毒理学方法进行实验室检查,结果:患者遗传损害、DNA合成与修复,DNA损伤等指标均发生异常改变,与正常人群比较差异均有统计学意义,皮肤组织中癌基因,抑癌基因表达异常,细胞增殖与凋亡紊乱,各指标在组间比较均有不同程度的差异并有统计学意义。结论:(1)砷致遗传物质发生异常改变以及影响DNA合成和修复,引起癌基因,抑癌基因蛋白的异常表达,细胞增殖与凋亡之间的正常比例发生改变,机体的自稳机制受到破坏,导致细胞过度分裂,持续增殖,是砷致病尤其引赶快细胞癌变的重要机理。(2)皮肤过度化可能是燃煤砷污染致皮肤癌变的先兆;P53^mt、PCNA、P16和CyclinD1蛋白的异常表达及Apoptosis的表达水平改变有望作为燃煤砷污染致皮肤癌变的预警标志;(3)SCE、CA和MN分析可作为检测细胞遗传学改变的早期生物指标;DPC则可作为中晚期严重损伤的标志物;SCGE作为一种早期、实用的方法应用于砷接触人群的DNA损伤监测具有实际意义。  相似文献
5.
胃癌与细胞凋亡   总被引:10,自引:10,他引:3  
细胞凋亡有其独特的形态学特点和生物学特点.肿瘤细胞也存在自发的细胞凋亡,只不过是肿瘤细胞凋亡与增殖的比例发生失调.肿瘤细胞存在的自发细胞凋亡受到药物、放射线、细胞因子、激素、基因编码等因素的影响[1].细胞凋亡已成为肿瘤治疗的新途径.胃癌是消化道常见...  相似文献
6.
AIM: To investigate the effects of lentivirus vector mediated short hairpin RNA interference targeting methionine adenosyltransferase 2β gene (LV-shMAT2B) on hepatocelluar carcinoma (HCC) cells. METHODS: We constructed four plasmids of RNA interference targeting the MAT2B gene. After LV-shMAT2B was transfected with L-02 cells and two kinds of HCC cells, cell viability and proliferation were measured with MTT and [3H]thymidine assays respectively. Flow cytometry was used to assess cell apoptosis. The level of S-adenosyl methionine (SAMe) in HepG2 cells was evaluated. The expressions of cyclin D1, cyclin D2, bcl-xL and bcl-xS were detected with western blot. RESULTS: We constructed LV-shMAT2B successfully. LV-shMAT2B was safe for human normal liver cells. LV-shMAT2B caused dramatic reduction in proliferation compared with controls in HCC cells Bel-7402 (P = 0.054) and HepG2 (P = 0.031). Flow cytometry analysis showed that cell apoptosis caused by LV-shMAT2B was greater in HCC cells Bel-7402 and HepG2 than in control induced by scrambled siRNA (P = 0.047), but apoptosis rates in L-02 induced by LV-shMAT2B and scrambled siRNA respectively had no significant difference. Moreover, LV-shMAT2B significantly suppressed expression of MAT2B leading to growth-inhibition effect on HCC cells by down-regulating cyclin D1. Apoptosis induced by LV-shMAT2B was involved indown-regulating bcl-xL and up-regulating bcl-xS. CONCLUSION: LV-shMAT2B can induce cell apoptosis and growth-inhibition in HCC cells. MAT2B may be a therapy target in HCC in the future.  相似文献
7.
华夏小葱含药血清对缺糖缺氧心肌细胞凋亡的影响   总被引:10,自引:1,他引:9  
目的:研究华夏小葱含药血清对缺糖缺氧乳鼠心肌细胞凋亡的影响.方法:采用差速贴壁法体外分离心肌细胞.调整细胞数随机分为4组:正常组、模型组、华夏小葱30%含药血清组、50 μg/ml依那普利组.采用MTT比色法检测细胞活力,分光光度法检测超氧化物歧化酶(SOD)、丙二醛(MDA)水平,流式细胞仪分析细胞早期凋亡的变化.结果:华夏小葱30%含药血清组与模型组比较,SOD有明显上升,MDA有明显下降(P均<0.05),其调亡率和依那普利组比较,无显著差异(P>0.05).结论:华夏小葱30%含药血清可以使缺糖缺氧心肌细胞SOD活性增加,MDA含量降低,并能抑制缺糖缺氧心肌细胞的凋亡.  相似文献
8.
AIM: TO investigate the effects of bombesin (BBS) and neurotensin (NTS) on apoptosis and colitis in an ulcerative colitis model.
METHODS: In this study, a total of 50 rats were divided equally into 5 groups. In the control group, no colitis induction or drug administration was performed. Colitis was induced in all other groups. Following the induction of colitis, BBS, NTS or both were applied to three groups of rats. The remaining group (colitis group) received no treatment. On the 11th d after induction of colitis and drug treatment, blood samples were collected for TNF-α and IL-6 level studies. Malondialdehyde (MDA), carbonyl, myeloperoxidase (MPO) and caspase-3 activities, as well as histopathological findings, evaluated in colonic tissues.
RESULTS: According to the macroscopic and microscopic findings, the study groups treated with BBS, NTS and BBS + NTS showed significantly lower damage and inflammation compared with the colitis group (macroscopic score, 2.1 ± 0.87, 3.7 ± 0.94 and 2.1 ± 0.87 vs 7.3 ± 0.94; microscopic score, 2.0 ± 0.66, 3.3 ± 0.82 and 1.8 ± 0.63 vs 5.2 ± 0.78, P 〈 0.01). TNF-α and IL-6 levels were increased significantly in all groups
compared with the control group. These increases were significantly smaller in the BBS, NTS and BBS + NTS groups compared with the colitis group (TNF-α levels, 169.69 ± 53.56, 245.86 ± 64.85 and 175.54 ± 42.19 vs 556.44 ± 49.82; IL-6 levels, 443.30 ± 53.99, 612.80 ± 70.39 and 396.80 ± 78.43 vs 1505.90 ± 222.23, P 〈 0.05). The colonic MPO and MDA levels were significantly lower in control, BBS, NTS and BBS + NTS groups than in the colitis group (MPO levels, 24.36 ± 8.10, 40.51 ± 8.67 and 25.83 ± 6.43 vs 161.47 ± 38.24; MDA levels, 4.70 ± 1.41, 6.55 ± 1.12 and 4.51 ± 0.54 vs 15.60 ± 1.88, P 〈 0.05). Carbonyl content and caspase-3 levels were higher in the colitis and NTS groups than in control, BBS and BBS + NTS groups (carbonyl levels, 553.99 ± 59.58 and 336.26 ± 35.72 vs 209.7  相似文献
9.
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP).
METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α), phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated.
RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α, PLA2 and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P 〈 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content, 8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P 〈 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P 〈 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes, respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h [P 〈 0.01, 0.00 (2.00)% vs 0.00 (0.00)%,  相似文献
10.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号-23

京公网安备 11010802026262号