全文获取类型
收费全文 | 1011篇 |
免费 | 86篇 |
国内免费 | 55篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 6篇 |
妇产科学 | 22篇 |
基础医学 | 169篇 |
口腔科学 | 4篇 |
临床医学 | 53篇 |
内科学 | 90篇 |
皮肤病学 | 7篇 |
神经病学 | 26篇 |
特种医学 | 12篇 |
外科学 | 64篇 |
综合类 | 156篇 |
预防医学 | 15篇 |
眼科学 | 4篇 |
药学 | 137篇 |
中国医学 | 10篇 |
肿瘤学 | 373篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 15篇 |
2016年 | 24篇 |
2015年 | 34篇 |
2014年 | 57篇 |
2013年 | 85篇 |
2012年 | 61篇 |
2011年 | 103篇 |
2010年 | 94篇 |
2009年 | 93篇 |
2008年 | 96篇 |
2007年 | 84篇 |
2006年 | 94篇 |
2005年 | 84篇 |
2004年 | 46篇 |
2003年 | 63篇 |
2002年 | 25篇 |
2001年 | 17篇 |
2000年 | 9篇 |
1999年 | 2篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 1篇 |
排序方式: 共有1152条查询结果,搜索用时 15 毫秒
141.
Fu-Liang Bai Yin-Hang Yu Hui Tian Gui-Ping Ren Hui Wang Bing Zhou Xiao-Hui Han Qing-Zhong Yu De-Shan Li 《Cancer biology & therapy》2014,15(9):1226-1238
Recombinant Newcastle disease virus (rNDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. In this study, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of inserting both interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV. We demonstrated that rNDV expressing TRAIL (rNDV-TRAIL) or both human IL-2 and TRAIL (rNDV-IL-2-TRAIL) significantly enhanced inherent anti-neoplastic of rNDV by inducing apoptosis. And we showed that apoptosis-related genes mRNA expression was increased after treated with rNDV-TRAIL or rNDV-IL-2-TRAIL compared with rNDV and rNDV-IL-2. We also demonstrated that both rNDV-IL-2 and rNDV-IL-2-TRAIL induced proliferation of the CD4+ and CD8+ in treated mice and elicited expression of TNF-α and IFN-γ antitumor cytokines. These mice treated with oncolytic agents exhibited significant reduction in tumor development compared with mice treated with the parental virus. In addition, experiments in both hepatocellular carcinoma and melanoma-bearing mice demonstrated that the genetically engineered rNDV-IL-2-TRAIL exhibited prolonged animals’ survival compared with rNDV, rNDV-IL-2, and rNDV-TRAIL. In conclusion, the immunotherapy and oncolytic virotherapy properties of NDV can be enhanced by the introduction of IL-2 and TRAIL genes, whose products initiated a broad cascade of immunological affects and induced tumor cells apoptosis in the microenvironment of the immune system. 相似文献
142.
[目的]研究肿瘤坏死因子相关凋亡诱导配体(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL)对人肺腺癌细胞株Calu-3增殖和凋亡的影响。[方法]用不同浓度TRAIL分不同时间段干预Calu-3细胞,MTT法检测细胞增殖抑制率,流式细胞仪检测细胞凋亡率。[结果]Calu-3细胞生长被TRAIL抑制,具有浓度和时间依赖性。TRAIL能诱导Calu-3细胞凋亡。[结论]TRAIL在体外具有抑制Calu-3细胞增殖,促使Calu-3细胞凋亡的作用。 相似文献
143.
Nianli Liu Chaohui Zuo Xiaohong Wang Tianran Chen Darong Yang Jing Wang Haizhen Zhu 《Oncotarget》2014,5(13):4959-4971
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive death ligand in targeted cancer therapy. Many cancer cells are refractory to TRAIL-induced cell death and the mechanisms underlying resistance are unclear. The molecular mechanisms of HCC and gastric cancer cells resistant to TRAIL-induced apoptosis were explored using molecular biological and immunological methods. In vivo experiments were conducted to study the effect of interferon stimulated gene 12a (ISG12a) on human liver cancer xenografts in mice. ISG12a decreases in TRAIL-resistant cancer cells. ISG12a regulates the sensitivity of cancer cells to TRAIL in vitro and in vivo. MicroRNA-942 (miR-942) is inversely correlated with ISG12a expression in cancer cells and tissues. Forced expression of miR-942 in TRAIL-sensitive cells significantly reduces endogenous ISG12a level and changes the TRAIL sensitive phenotype to a resistant one. Knockdown of miR-942 expression in TRAIL-resistant cells restores the expression of ISG12a and sensitizes the cells to TRAIL treatment. AKT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Downregulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype of cancer cells and favors cancer cell survival. MiR-942 may offer a novel drug response marker with important implications in designing new therapeutics for TRAIL resistant tumors. 相似文献
144.
Jinkwon Kim Tae-Jin Song Seung-Hee Yang Ok-Hee Lee Hyo Suk Nam Young Dae Kim Eun Hee Kim Hye Sun Lee Chung Mo Nam Ji Hoe Heo 《Clinical biochemistry》2013
Objectives
Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. We investigated whether plasma OPG levels were associated with the presence and severity of cerebral atherosclerosis.Design and methods
We used an enzyme-linked immunosorbent assay to measure the plasma OPG levels of 107 patients with acute cerebral infarction. We compared the plasma OPG levels according to the presence and number of arteries with cerebral atherosclerosis (≥ 50% stenosis).Results
Of 107 patients, 73 (68.2%) had cerebral atherosclerosis. OPG levels were increased in patients with cerebral atherosclerosis (374.69 ± 206.48 vs 261.17 ± 166.91 pg/mL, p = 0.006). OPG levels showed positive correlation with the number of cerebral arteries with atherosclerosis (Spearman's rho = 0.342, p < 0.001). After adjustment for vascular risk factors, OPG > 229.9 pg/mL was independently associated with the presence [OR 4.61, 95% CI 1.57–13.55, p = 0.005, binary logistic regression] of cerebral atherosclerosis and number [OR 3.20, 95% CI 1.26–8.12, p = 0.014, ordinal logistic regression] of arteries with cerebral atherosclerosis.Conclusions
Plasma OPG levels were significantly associated with the presence and severity of cerebral atherosclerosis. This finding suggests that plasma OPG might have a role in cerebral atherosclerosis. 相似文献145.
Influence of the corticospinal tract on the cutaneous silent period: a study in patients with pyramidal syndrome 总被引:1,自引:0,他引:1
Gilio F Bettolo CM Conte A Iacovelli E Frasca V Serrao M Giacomelli E Gabriele M Prencipe M Inghilleri M 《Neuroscience letters》2008,442(2):109-113
Celecoxib is a cyclooxygenase 2-selective nonsteroidal anti-inflammatory drug (NSAID) that exhibited therapeutic activity in cancer. In this study three malignant glioma, U87-MG, U251 and A172, were treated with celecoxib, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the combination of both. Single treatment with celecoxib (25-100muM) for 24h resulted in a concentration-dependant decrease of cellular viability in U87-MG, U251 and A172. Combining subtoxic concentrations of celecoxib with TRAIL strongly increased cell death in human malignant glioma cells. After 8h treatment with celecoxib we found down-regulation of the inhibitor of apoptosis protein survivin that was mediated by proteasomal degradation. In addition, over-expression of survivin not only attenuated celecoxib-induced cytotoxicity but also cytotoxicity induced by the combination of celecoxib and TRAIL. Taken together, in malignant glioma survivin is a key regulator in celecoxib- and TRAIL-celecoxib-mediated cell death. 相似文献
146.
Barbara Toffoli Stella Bernardi Riccardo Candido Nicoletta Sabato Renzo Carretta Federica Corallini Paola Secchiero Giorgio Zauli Bruno Fabris 《Molecular and cellular endocrinology》2011
Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin–angiotensin system (RAS). 相似文献
147.
148.
目的 观察不同浓度的肿瘤坏死因子相关凋亡诱导配体(TRAIL)和顺铂对Hela细胞的诱导凋亡作用.方法 采用不同浓度的TRAIL作用于Hela细胞24 h,TRAIL 100 ng/mL、顺铂10 μmol/L及两者联合作用于细胞24 h,应用ELISA方法检测细胞凋亡率.结果 不同浓度的TRAIL作用于细胞后,细胞凋... 相似文献
149.
目的:探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因1 525位点G/A、1 595位点C/T单核苷酸多态性(SNP)与妊娠期糖尿病(GDM)的关系及TRAIL在GDM发生中的可能作用。方法:利用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)的方法检测TRAIL基因1 525位点G/A、1 595位点C/T多态性,并测定空腹血糖(FPG)、空腹胰岛素(FINS)等生化指标。计算相应的基因型频率和等位基因频率,通过χ2检验和方差分析,分析TRAIL基因型和等位基因与GDM及各生化指标的相关性。结果:GDM组TRAIL基因型频率和等位基因频率高于正常妊娠组(分别为P<0.05和P<0.01);GDM组GA/CT、AA/TT基因型FPG、FINS均高于GG/CC基因型(P<0.05)。结论:TRAIL基因1 525位点G/A、1 595位点C/T单核苷酸多态性与妊娠期糖尿病密切相关,可能参与GDM的发病机制。 相似文献
150.
目的 构建肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因修饰的脐带间充质干细胞(TRAIL-MSCs),并检测其联合地塞米松(DEX)对急性B淋巴细胞白血病(Nalm-6)细胞的影响。方法 通过慢病毒载体将SPD-TRAIL基因转染UC-MSCs构建TRAIL-MSCs,使其能够表达十二聚体TRAIL蛋白(dTRAIL)。通过CCK-8法、流式细胞术、显微镜光镜下观察细胞形态及密度检测UC-MSCs、TRAIL-MSCs、DEX(25 μmol/L)、DEX(25 μmol/L)+UC-MSCs组和DEX(25 μmol/L)+TRAIL-MSCs对Nalm-6细胞增殖、凋亡的影响;通过实时荧光定量PCR及Western blotting法检测各组Nalm-6细胞表面DR4、DR5 mRNA和蛋白表达。结果 成功构建了能够稳定表达dTRAIL蛋白的TRAIL-MSCs工作库细胞。与对照组比较,UC-MSCs、TRAIL-MSCs显著抑制Nalm-6细胞增殖(P<0.01),但抑制率均在30%以下,DEX抑制率约为43%,而DEX联合TRAIL-MSCs抑制率达85%,与TRAIL-MSCs和DEX组比较差异显著(P<0.01)。显微镜下观察结果显示,不同处理方式对肿瘤细胞Nalm-6均有一定的杀伤作用,其中以DEX与TRAIL-MSCs联合用药组的杀伤作用最明显。TRAIL-MSCs可以促进Nalm-6细胞凋亡,凋亡率达10%,DEX组凋亡率达到15%,与对照组比较有显著差异(P<0.05、0.01);而DEX+TRAIL-MSCs组凋亡率达36%,与DEX和TRAIL-MSCs组比较有显著差异(P<0.01)。与对照组比较,TRAIL-MSCs组DR4、DR5 mRNA表达量显著降低(P<0.01);DEX可以促进DR4、DR5 mRNA表达,与对照组比较差异显著(P<0.01);DEX+TRAIL-MSCs组较DEX组DR4、DR5 mRNA表达均显著降低(P<0.01);各组蛋白检测结果与mRNA结果基本一致。结论 DEX可以显著提高TRAIL-MSCs对Nalm-6细胞的杀伤作用,或将成为一种颇具潜力的血液肿瘤治疗新手段;其机制与DEX显著提高DR4、DR5表达,增强Nalm-6细胞对TRAIL蛋白的敏感性相关。 相似文献