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1.
克雷伯菌临床菌株中1类整合子相关基因的分析   总被引:17,自引:0,他引:17  
目的:研究多重耐药克雷伯菌中1类整合子基因及相关的sull和qacEΔ1基因的携带情况.方法:K-B法做耐药菌株的药敏试验.PCR扩增检测intll整合酶基因,sull和qacEZX1基因.结果:克雷伯菌多为3种或3种以上抗生素耐药,其耐药表型大多为对氨苄青霉素/克拉维酸、庆大霉素、头孢唑啉和哌拉西林耐药,且与1类整合子的存在密切相关.整合酶intI1基因阳性率为80%(48/60);1类整合子相关的sull和qacE△1基因的阳性率分别为94%(45/48)和90%(43/48).结论:克雷伯菌的多重耐药与1类整合子密切相关.sull和qacE△1基因可以作为1类整合子的标志基因。  相似文献
2.
浙贝母散剂逆转急性白血病多药耐药的临床研究   总被引:16,自引:0,他引:16  
目的初步探讨浙贝母散剂和化疗合用时是否能起到逆转P170高表达的作用及其临床应用前景.方法.应用流式细胞仪检测急性白血病患者P糖蛋白(P170)表达,并对阳性患者随机分组,用浙贝母散剂加联合化疗进行逆转多药耐药的临床研究.结果.浙贝母散剂在临床安全剂量下,与常规化疗方案合用,仍可逆转P170高表达;浙贝母散剂与急性白血病(AL)常规化疗方案合用可以降低骨髓原始细胞百分比,有可能提高临床治疗完全缓解率.结论.浙贝母散剂可能成为一种安全有效的多药耐药逆转剂,在P170高表达的急性白血病中有较大的临床意义及推广价值.  相似文献
3.
P—糖蛋白及多药耐药相关蛋白在胃癌中的表达与意义   总被引:16,自引:1,他引:15  
目的:了解P-糖蛋白(Pgp)及多药耐药相关蛋白(MRP)在胃癌中的表达与意义,方法;采用免疫组化SABC法。结果:在43例胃癌中,Pgp及MRP阳性者分别为13例(30.2%)22例(51.2%)在43相应癌旁组织中分别为8例(18.6%),17例(39.5%)而在30例胃炎组织中则分别为5例(16.7%),9例(30.0%)Pgp与MRP表达均阳性者,癌组织4例(9.3%)癌旁组织1例(2.3  相似文献
4.

Background  Chemotherapy is the most frequently adopted adjuvant therapy of pancreatic ductal adenocarcinoma (PDAC), but the development of drug resistance reduces its effectiveness. Clarification of the mechanism of multidrug resistance (MDR) development in PDAC is needed to improve the therapeutic effect of chemotherapy. This study was aimed to investigate the molecular mechanism of MDR of PDAC and to identify genes associated with MDR development.
Methods  The gene expression profiles of cell line SW1990 and three drug-selected pancreatic chemoresistant sub-lines, SW1990/5-Fu, SW1990/ADM and SW1990/GEM, were obtained using an oligonucleotide microarray (Affymetrix HG U133 2.0 plus) that contained approximately 38 000 human genes. The microarray results were validated by real-time quantitative polymerase chain reaction and Western blot analysis.
Results  There were 165 genes and expressed sequence tags, some of which have never been linked to drug resistance, that were up- or down-regulated at least 2-fold in all resistant sub-lines when compared with SW1990. According to Gene Ontology annotation, differentially expressed genes related to MDR in pancreatic cancer belong to many functional families and with diverse biological processes. Genes related to antioxidant activity, apoptosis, the cell cycle, signal transduction and intracellular adhesion may undergo epigenetic changes preceding MDR development. A hierarchical clustering was conducted and several interesting clusters were discovered that may be primarily related to cell cycle and developmental regulation. A prediction rule was built from the expression profiles of 117 genes after support vector machine (SVM) analysis, and the prediction result was examined by cytotoxic testing. As a result, a differential gene expression pattern was constructed in multidrug resistant pancreatic cancer cells.
Conclusions  The findings of this study prove that construction of a chemoresistance prediction rule, based on gene expression patterns, is practical. These data provide new insights into the molecular mechanism of pancreatic cancer MDR development and may be useful for the detection and treatment of MDR in pancreatic cancer patients.

  相似文献
5.
目的探讨人参皂甙Rg3对耐顺铂(CDDP)人肺腺癌细胞系A549DDP的逆转作用及其机理.方法以A549DDP及其亲本细胞A549为研究对象,MTT法观察Rg3对A549DDP耐药的逆转作用,采用免疫组化及RT-PCR方法分别在蛋白质和mRNA水平检测耐药相关蛋白MDR1、MRP、LRP表达.结果 MTT法显示低细胞毒浓度Rg3(10 μmol)有效逆转A549DDP细胞耐药7.3倍,而20、30 μmol Rg3分别逆转耐药1.3、1.2倍;10 μmol Rg3预处理A549DDP细胞12、24、36及48 h后分别逆转耐药1.0、1.6、7.6及10.4倍,表明Rg3逆转耐药呈时间依赖性.免疫组化和RT-PCR显示:A549DDP细胞MDR1、MRP、LRP呈过量表达,以Rg3(10 μmol)预处理A549DDP 12、24、36及48 h后,MDR1、MRP表达减弱,呈时间依赖性,而LRP表达无明显时间依赖性.结论 Rg3具有中度逆转肿瘤耐药作用,并呈时间依赖性.  相似文献
6.
ADM诱导人肝癌细胞株多重抗药性的形成   总被引:14,自引:1,他引:13  
目的:建立人肝癌耐药细胞模型,研究其多药耐药机制。方法:对人肝癌细胞株BEL-7404采用阿霉素浓度递增法及高浓度间歇诱导法,建立人肝癌耐药细胞BEL-740/ADM,用MTT法检测其检测其耐药性,用免疫细胞化学法检测细胞p-糖蛋白(p-gp)及多药耐药相关蛋白(MRP)的表达,结果:用此方法建立的肝癌耐药细胞模型BEL-7404/ADM经MTT法检测其对阿霉素的IC50较亲本细胞BEL-7404增加100倍,并对多种抗癌药物产生交叉耐受性。细胞p-gp及MRP表达较亲本细胞有显著增加(P<0.01),p-pg阳性率为68.7%,MRP阳性率为53.5%,结论:BEL-7404/ADM是一个多药耐药模型,其多药耐药性与p-gp、MRP高度表达有关。  相似文献
7.
人肺腺癌多药耐药细胞系的建立及其生物学特征   总被引:14,自引:2,他引:12  
目的 建立人肺腺癌多药耐药细胞系。方法 以顺铂为诱导药物,人肺腺癌细胞系SPC-A-1为诱导对象,采用大剂量冲击与逐步增加剂量相结合的方法,诱导建立人肺腺癌多药耐药细胞系SPC-A-1/CDDP;MTT法测定药物敏感性,透射和扫描电镜观察形态变化,常规染色体检测分析染色体变化。结果 用192d建成人肺腺癌多药耐药细胞系SPC-A-1/CDDP,它对顺铂的耐药指数为11.2,对顺铂、5-氟尿嘧啶、丝裂霉素、长春新碱和足叶乙甙等药物有不同程度的耐药性,但对羧基喜树碱无耐药性,电镜观察可见SPC0-A-1/CDDP细胞胞核不规则,较大,有丰富的微绒毛。结论 本研究建立了稳定的人肺腺癌多药耐药细胞系(SPC-A-1/CDDP),可应用于下游实验。  相似文献
8.
Background Intractable epilepsy may be due to multidrug resistance induced by conventional antiepileptic drugs. The phenomenon is sometimes associated with an overexpression of multidrug resistance gene 1 ( MDR1 ). The purpose of this study was to determine if the overexpression of MDR1 could be induced in astrocytes from rat brains in vitro using antiepileptic drugs.Methods Astrocyte cell cultures from postnatal Wistar rats (within 24 hours of birth ) were established. Different concentrations of the antiepileptic drugs phenytoin, phenobarbital,carbamazepine, and valproic acid were added to the cultures for 10, 20, or 30 days. The expression of P-glycoprotein (Pgp), the protein product of MDR1, was investigated with immunocytochemistry.Results Less than 5% of normal, untreated astrocytes had detectable Pgp staining at any time point. Phenytoin, phenobarbital, carbamazepine, and valproic acid induced the overexpression of Pgpin astrocytes in a dose- and time-dependent manner. Significantly higher levels of Pgp staining were detected at therapeutic concentrations of certain antiepileptic drugs (20 μg/ml phenobarbital, 40μg/mlphenobarbital, and 20μg/ml phenytoin) on day 30. Upregulation of Pgp was detected when using higher concentrations of phenytoin, phenobarbital, and valproic acid on day 20 and when using higher concentrations of any of the four antiepileptic drugs on day 30.Conclusions Treatment with antiepileptic drugs may contribute to the overexpression in astrocytes of MDR1 and its protein product, Pgp. The mechanism leading to MDR must be considered in patients under qoinq lonq-term treatment with antiepileptic drugs.  相似文献
9.
多药耐药相关蛋白在胃癌中表达的意义   总被引:12,自引:0,他引:12  
应用免疫组化LSAB法对52例胃癌患者检测耐药相关蛋白(MRP)在胃癌组织中的表达。结果发现52例胃癌中20例阳性,阳性表达率为38.5%。MRP在肿瘤细胞膜上和胞浆内均有表达,且以胞浆内(粗颗粒状)更明显。晚期胃癌(Ⅲ、Ⅳ期)阳性率为60%,显著高于Ⅰ、Ⅱ期早期胃癌的18.5%表达率(P<0.01)。MRP阳性者平均生存期(20.9±20.7月)和5年生存率(10%)显著低于阴性者(分别为48.5±22.7月与65.6%,均P<0.01)。提示,MRP在胃癌中的表达与预后密切相关,其可能是内源性耐药的重要机制之一。  相似文献
10.
雄黄诱导K562/ADM细胞凋亡的研究   总被引:11,自引:0,他引:11  
探讨雄黄诱导多药耐药细胞K562/ADM细胞凋亡的能力,并初步探讨其分子机制,方法:采用荧光标记形态学观察,流式细胞仪进行DNA分析及测定细胞表面p-gp的表达。结果显示:雄黄能明显诱导K562/ADM细胞凋亡,且在48h后p-gp的表达下调。  相似文献
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