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1.
郑茂  邹玉  王洁莹  况南珍  傅颖媛 《安徽医药》2022,26(11):2198-2202
目的探讨瑞香素(DAP)通过含半胱氨酸的天冬氨酸蛋白水解酶(caspase)通路对胶原诱导性关节炎(CIA)大鼠成纤维样滑膜细胞(FLS)增殖与凋亡的影响。方法体外培养 CIA-FLS,选取对数生长期细胞以不同浓度 DAP(0、5、10、20、40、80 mg/  相似文献   
2.
张露  陈媛  李俊良  张华  谢春 《现代预防医学》2022,(16):3019-3024
目的 探讨姜黄素对氯化铝染毒所致NG108 - 15细胞凋亡的影响及其机制,为铝致学习记忆损伤的治疗提供参考。方法 取对数生长期NG108 - 15细胞,随机分为空白对照组、DMSO组(溶剂对照)、姜黄素组(16 μmol/L姜黄素)、铝组(160 mg/L氯化铝染毒 )、铝+姜黄素组(160 mg/L氯化铝染毒24 h后,给予16 μmol/L姜黄素处理24 h)。收集各组细胞,采用吖啶橙/嗅化乙锭(AO/EB)双荧光染色观察细胞凋亡形态,计数凋亡细胞数并计算凋亡率;流式细胞术检测细胞凋亡率, qRT - PCR检测细胞中PKC、NMDAR1、NMDAR2B 的mRNA表达水平,western blot检测细胞中凋亡相关蛋白(caspase3、Bax)和PKC、NMDAR1、NMDAR2B的蛋白表达水平。多组间均数的比较采用单因素方差分析(one - way ANOVA),组间两样本均数的比较采用LSD法。结果 与空白对照组相比,铝染毒组的caspase3、Bax蛋白表达水平升高(t = - 5.547、 - 4.948,P<0.001),PKC、NMDAR1、NMDAR2B的mRNA(t = 4.926,P = 0.003;t = 6.330,P<0.001;t = 4.224,P = 0.019)和蛋白(t = 20.638,P<0.001;t = 4.509,P<0.001;t = 17.388,P = 0.002)表达水平降低, AO/EB染色和流式细胞术结果均表明细胞凋亡率升高(t = - 5.153、 - 7.390,P<0.001);加入姜黄素处理后,与铝染毒组相比,铝+姜黄素组的caspase3、Bax蛋白表达水平降低(t = 2.930,P = 0.006;t = 4.907,P<0.001),PKC、NMDAR1、NMDAR2B 的mRNA(t = - 10.337、 - 6.621、 - 6.847,P<0.001)和蛋白(t = - 30.551、 - 7.451、 - 26.294,P<0.001)表达水平升高,AO/EB染色和流式细胞术结果均表明细胞凋亡率降低(t = 2.707,P = 0.01;t = 4.632,P<0.001)。结论 上调PKC - NMDAR信号通路表达,可能是姜黄素减轻氯化铝染毒所致NG108 - 15细胞凋亡的机制之一。  相似文献   
3.
Emerging evidence has shown that the therapy-induced senescent growth arrest in cancer cells is of durable nature whereby a subset of cells can reinstate proliferative capacity. Promising new drugs named senolytics selectively target senescent cells and commit them into apoptosis. Accordingly, senolytics have been proposed as adjuvant cancer treatment to cull senescent tumor cells, and thus, screening for agents that exhibit senolytic properties is highly warranted. Our study aimed to investigate three agents, sorafenib, rapamycin, and venetoclax for their senolytic potential in doxorubicin-induced senescence in HCT116 cells. HCT116 cells were treated with one of the three agents, sorafenib (5 µM), rapamycin (100 nM), or venetoclax (10 µM), in the absence or presence of doxorubicin (1 µM). Senescence was evaluated using microscopy-based and flow cytometry-based Senescence-associated-β-galactosidase staining (SA-β-gal), while apoptosis was assessed using annexin V-FITC/PI, and Muse caspase-3/-7 activity assays. We screened for potential genes through which the three drugs exerted senolytic-like action using the Human Cancer Pathway Finder PCR array. The three agents reduced doxorubicin-induced senescent cell subpopulations and significantly enhanced the apoptotic effect of doxorubicin compared with those treated only with doxorubicin. The senescence genes IGFBP5 and BMI1 and the apoptosis genes CASP7 and CASP9 emerged as candidate genes through which the three drugs exhibited senolytic-like properties. These results suggest that the attenuation of doxorubicin-induced senescence might have shifted HCT116 cells to apoptosis by exposure to the tested pharmacological agents. Our work argues for the use of senolytics to reduce senescence-mediated resistance in tumor cells and to enhance chemotherapy efficacy.  相似文献   
4.
《Pancreatology》2022,22(1):74-82
ObjectivePost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP and the mechanism is not fully understood. This study evaluated the changes in the inflammatory response, cellular apoptosis, and tight junction integrity in a rat model of pancreatitis to explore the underlying mechanism.MethodsPEP was induced in rats by retrograde biliopancreatic ductal infusion of contrast agents or saline. Pancreatic tissues were harvested and evaluated by histopathologic, immunohistochemical, immunofluorescence, and Western blot analyses. In addition, amylase and proinflammatory cytokines in plasma were quantified by ELISA assay.ResultsPEP rats developed more severe acute pancreatitis than the sham group after injection of the contrast agent or isotonic saline. PEP rats exhibited increased tissue damage, plasma amylase, proinflammatory cytokines, necrosis, inflammatory infiltrates, apoptosis, and tight junction disruption. At the molecular level, contrast agent and isotonic saline-injected PEP rats demonstrated elevated NF-κB p65 and STAT3 pathways activation, altered expression and activation of apoptosis-related proteins, and suppressed expression of tight junction molecules. However, the contrast agent concentration had no effect on these changes.ConclusionsIn models of acute pancreatitis induced using contrast agent and hydrostatic pressure, the contrast agent and high hydrostatic pressure easily induced the inflammatory response, apoptosis, and tight junction disruption. It is noteworthy that no significant difference in damaged pancreatic acinar cells was observed with different concentrations of the contrast agent.  相似文献   
5.
目的 探讨间歇低氧大鼠淋巴细胞促进脑血管内皮细胞内质网应激凋亡作用及机制。方法 取SD雄性大鼠30只,分为正常对照组、间歇低氧组、抗低氧组,每组各10只; 抗低氧组、间歇低氧组建立间歇低氧大鼠模型,并分别于间歇低氧前半小时腹腔注射100 mg/kg超氧阴离子清除剂和等量生理盐水,1次/d,然后间歇低氧干预8 h/d; 正常对照组维持常氧量,干预6周; 各组干预后分离淋巴细胞,测定CD4+、CD8+ T细胞凋亡率; 取对数期内皮细胞RBE4,与各组分离淋巴细胞共培养,命名为正常对照RBE4组、间歇低氧RBE4组、抗低氧RBE4组; 4 h后测定培养基上清液中超氧化物歧化酶(Superoxide dismutase,SOD)及丙二醛(Malonaldehyde,MDA)水平、内皮细胞凋亡率、内皮细胞中C增强子结合蛋白同源蛋白(Cenhancer binding protein homologous protein,CHOP)、葡萄糖调节蛋白78(Glucose regulatory protein 78,GRP78)、半胱氨酸天冬氨酸蛋白水解酶-3(Cysteine containing aspartate-specific proteases-3,Caspase-3)mRNA及蛋白水平。结果 与正常对照组比较,间歇低氧组、抗低氧组CD4+、CD8+ T细胞凋亡率降低,且间歇低氧组低于抗低氧组(P<0.05); 与正常对照RBE4组比较,间歇低氧RBE4组、抗低氧RBE4组上清液中SOD水平降低、MDA水平增高、RBE4凋亡率增高、CHOP,Caspase-3 mRNA及蛋白水平升高、GRP78 mRNA及蛋白水平降低(P均<0.05); 与抗低氧RBE4组比较,间歇低氧组SOD水平降低、MDA水平增高、RBE4凋亡率增高、CHOP,Caspase-3 mRNA及蛋白水平升高、GRP78 mRNA及蛋白水平降低(P均<0.05)。结论 间歇低氧大鼠淋巴细胞促进脑血管内皮细胞凋亡可能通过激发内质网应激而发挥作用。  相似文献   
6.
目的:探究七氟烷对人舌鳞状细胞癌Tca-8113细胞的凋亡机制。方法:用2~10μmol/L七氟烷作用体外培养人舌鳞状细胞癌Tca-8113细胞。MTT实验检测细胞活力;Hochest/PI双染法以及流式细胞术检测细胞凋亡;Western blot法检测MAPK/STAT3信号通路中相关蛋白表达含量的变化以及通过加入MAPK抑制剂检测MAPK与STAT3信号通路的关系。结果:七氟烷对Tca-8113细胞具明显的杀伤效应,IC50=8μmol/L。七氟烷能够诱导Tca-8113细胞凋亡,促进Bax、cle-cas-3、cle-PARP、p-p38及p-JNK蛋白的表达,抑制Bcl-2、p-STAT3蛋白的表达;加入MAPK抑制剂后,细胞中p-p38、p-JNK、cle-cas-3及cle-PARP表达量降低,p-STAT3、p-ERK表达量增多。结论:七氟烷可能通过调控MAPK/STAT3信号通路从而导致Tca-8113细胞发生凋亡。  相似文献   
7.
Cerebral ischemia seriously affects the quality of life and health of human worldwide. W026B is a newly synthesized lignan derivative that has a protective effect on the focal cerebral ischemia/reperfusion model, while it is unclear whether W026B has a cerebral protective effect on the model of global cerebral ischemia/reperfusion (GCI/R). In this study, we investigated the protective effect of W026B on the four-vessel occlusion GCI/R model. The results showed that W026B obviously increased the survival rate of rats during 7 d after GCI/R and significantly improved neurological deficits within 7 d after GCI/R. It evidently enhanced the number of survival neurons in the hippocampus of GCI/R rats. Furthermore, W026B notably lowered the level of ROS, and increased the activity of SOD in the hippocampus of GCI/R rats. Moreover, it also decreased the expression of NF-κB p65 and the level of IL-6 apparently. In addition, W026B evidently lowered the activity of caspase-3. In conclusion, this study firstly proves that W026B has the protective effect on GCI/R rats. Its cerebral protective effect maybe related to the inhibition of oxidative stress, inflammatory response, and cell apoptosis during GCI/R. These results provide new evidence with the protective effect of W026B on cerebral ischemia/reperfusion injury.  相似文献   
8.
目的:研究鱼藤素(De)诱导SGC-7901胃癌细胞凋亡的其作用机制。方法:运用CCK-8细胞活力检测法考察不同浓度(10、20、40、60、80、100 mol/L)鱼藤素作用24、48 h对SGC-7901胃癌细胞的细胞毒性;将SGC-7901胃癌细胞分为对照组及20、40 mol/L鱼藤素药物组,给药作用24 h后,蛋白质印迹法检测p-AKTThr308、叉头框蛋白O1(FoxO1)、B淋巴细胞瘤-2基因(Bcl-2)等蛋白的表达水平;运用蛋白激酶B(AKT)基因转染使SGC-7901胃癌细胞中AKT过表达,然后给予20、40 mol/L鱼藤素给药作用24 h,以未用AKT基因转染的SGC-7901胃癌细胞作为对照组蛋白质印迹法检测p-AKTThr308、FoxO1、Bcl-2等蛋白的表达水平,实时荧光定量PCR(RT-qPCR)检测FoxO1、Bcl-2、Bax mRNA的表达水平。结果:不同浓度的鱼藤素对SGC-7901胃癌细胞均具有一定的细胞毒性;20、40 mol/L鱼藤素给药作用24 h能够显著降低SGC-7901胃癌细胞中p-AKTThr308、Bcl-2等蛋白的表达水平,升高FoxO1的表达水平;与对照组比较,AKT基因转染后,SGC-7901胃癌细胞中p-AKTThr308、Bcl-2等蛋白表达水平升高,FoxO1蛋白表达降低,与模型组比较,20、40 mol/L鱼藤素给药作用后能够降低p-AKTThr308、Bcl-2等蛋白的表达水平,降低Bcl-2 mRNA的表达水平,升高FoxO1及Bax的表达水平。结论:鱼藤素能够通过作用于AKT/FoxO1信号通路诱导胃癌细胞SGC-7901凋亡。  相似文献   
9.
《Saudi Pharmaceutical Journal》2022,30(11):1561-1571
ObjectivesHuangpu Tongqiao Capsule (HPTQC) is a traditional Chinese medicine (TCM) that has been used to treat Alzheimer's disease (AD). This study was to explore the pharmacological action and molecular mechanism of HPTQC in the treatment of AD.MethodsThe possible targets of HTPQC were predicted by the molecular docking technique. Intraperitoneal injection of D-galactose and bilateral injection of Aβ25-35 in hippocampus induced AD rat model. Morris water maze was used to observe learning and memory function. The primary hippocampal neurons were induced by Aβ25-35. Moreover, the apoptosis rate of hippocampal nerve cells was detected through AnnexinV/PI double standard staining. The mRNA and protein levels of GRP78, CHOP, Caspase 12, Caspase 9, and Caspase 3 were detected by PCR and western blot.ResultsThe prediction results suggest that HPTQC may act on GRP78. HPTQC significantly improved the learning and memory function, and decreased neuronal apoptosis in vivo and in vitro. In addition, HPTQC could decrease the mRNA and protein expression levels of GRP78, CHOP, Caspase12, Caspase9, and Caspase3, and the effect trend was consistent with the specific inhibitor of GRP78.ConclusionsHPTQC has a neuroprotective effect against AD by inhibiting the apoptosis pathway mediated by endoplasmic reticulum stress.  相似文献   
10.
目的探讨干扰LINC00707对食管癌细胞生物行为的影响及分子机制。方法选取51例食管癌患者癌组织及癌旁正常组织,用实时荧光定量-聚合酶链反应(RT-qPCR)检测LINC00707和miR-382-5p的表达水平;将食管癌细胞EC9706随机分为对照(con)组、si-LINC00707组、si-NC组、miR-382-5p组、miR-NC组、anti-miR-382-5p组、anti-miR-NC组、si-LINC00707+anti-miR-382-5p组;用四甲基偶氮唑盐(MTT)比色法检测细胞活性;克隆形成实验检测细胞克隆形成数;流式细胞术检测细胞凋亡率;划痕实验检测细胞迁移距离;Western印迹法检测蛋白表达;双荧光素酶报告实验检测LINC00707和miR-382-5p的靶向关系。结果与癌旁正常组织相比,食管癌组织中LINC00707表达水平升高,miR-382-5p表达水平降低,差异有统计学意义(P<0.05);且LINC00707和miR-382-5p表达水平呈负相关(P<0.05)。干扰LINC00707或过表达miR-382-5p后,EC9706细胞活性降低,克隆形成数减少,细胞凋亡率升高,细胞迁移距离缩短,Bax表达水平升高,Bcl-2表达水平降低,差异有统计学意义(P<0.05)。抑制miR-382-5p表达与过表达miR-382-5p对EC9706细胞的作用相反。且抑制miR-382-5p表达逆转了干扰LINC00707对EC9706细胞的作用。LINC00707靶向调控miR-382-5p。结论干扰LINC00707可能通过上调miR-382-5p抑制食管癌细胞的恶性生物学行为。  相似文献   
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