全文获取类型
收费全文 | 220篇 |
免费 | 12篇 |
国内免费 | 2篇 |
专业分类
儿科学 | 10篇 |
妇产科学 | 6篇 |
基础医学 | 16篇 |
口腔科学 | 1篇 |
临床医学 | 9篇 |
内科学 | 54篇 |
皮肤病学 | 11篇 |
神经病学 | 4篇 |
特种医学 | 58篇 |
外科学 | 9篇 |
综合类 | 14篇 |
预防医学 | 9篇 |
眼科学 | 3篇 |
药学 | 16篇 |
肿瘤学 | 14篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 6篇 |
2013年 | 7篇 |
2012年 | 5篇 |
2011年 | 6篇 |
2010年 | 6篇 |
2009年 | 13篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 6篇 |
2005年 | 9篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 7篇 |
1997年 | 12篇 |
1996年 | 10篇 |
1995年 | 12篇 |
1994年 | 8篇 |
1993年 | 14篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 10篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有234条查询结果,搜索用时 15 毫秒
21.
目的:应用RNA干扰技术设计构建针对血管内皮细胞生长因子受体KDR的小干扰RNA,并观察脂质体转染肺癌细胞A549后的干扰效果。方法:实验于2005-03/2006-01在沈阳医学院生物化学及分子生物学教研室完成。①设计针对KDR编码区有短发夹结构的3条mRNA序列,经退火成互补双链,克隆到pGCsi.H1/neo/GFP载体中构建3个重组质粒,分别命名为KDR-siRNA1、KDR-siRNA2和KDR-siRNA3。②设立5组:小干扰RNA组,分别转染KDR-siRNA1、KDR-siRNA2和KDR-siRNA3;阳性对照组,转染pGCsi.H1/neo/siGFP,该质粒载体中的插入序列为针对绿色荧光蛋白的小干扰RNA,不干扰待研究的内源性基因;阴性对照组,转染pGCsi.H1/neo/GFP/NON,该载体为不干扰任何内源性基因的小干扰RNA;空白对照组,转染pGCsi.H1/neo/GFP空载体;正常对照组,不进行任何转染。③对重组质粒进行酶切鉴定、DNA测序分析;脂质体法转染质粒至肺癌A549细胞株后,实时定量PCR检测KDRmRNA的水平变化;细胞计数法绘制细胞生长曲线。结果:①小干扰RNA表达载体的鉴定:KDR-siRNA1、KDR-siRNA2和KDR-siRNA3表达载体用限制性内切酶NdeⅠ和SmaⅠ进行单酶切后,均产生约713bp、5480bp和2403bp、3790bp两个片段,与预期结果相同。测序结果与设计的编码相应短发夹状KDR-小干扰RNA的寡核苷酸序列一致,证明KDR-小干扰RNA真核表达载体构建成功。②KDR-小干扰RNA对A549细胞中KDRmRNA水平的影响:与阳性对照组、阴性对照组、空白对照组和正常对照组的A549细胞相比,KDR-siRNA1,2,3表达载体转染后的A549细胞KDR基因表达水平均明显受到抑制,抑制率分别为64%、81%和72%,其中以KDR-siRNA2抑制作用最为明显。③KDR-小干扰RNA对A549细胞生长的影响:阳性对照组、阴性对照组、空白对照组、正常对照组的A549细胞生长趋势较为一致,且生长速度均明显高于转染3种KDR-小干扰RNA表达载体的A549细胞,从接种第2天开始差异有显著性意义(t=15.29~17.65,P均<0.01)。结论:血管内皮细胞生长因子受体KDR靶向RNA干扰重组质粒构建成功,该载体能有效抑制肺癌A549细胞KDR基因表达与细胞增殖。 相似文献
22.
23.
24.
BACKGROUND: Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE: To evaluate the clinical, radiological and surgical outcome of 40 focal "intrinsic" brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS: A total of 40 focal ‘intrinsie’ ("expanding variety") tumors have been operated over a period of 8.5-years (January 1998-June 2007). Our criteria included patients with (1) well-defined gadolinium enhancing tumor, (2) relatively long duration of symptoms (〉 six months) and (3) good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS: The "intrinsic" brainstem tumors were classified into three types: Expanding, diffuse infiltrative and pure ventral varieties. 相似文献
25.
26.
Krutchen AE; Bjarnason H; Stackhouse DJ; Nazarian GK; Magney JE; Hunter DW 《Radiology》1996,200(1):159
27.
Cyclic neutropenia (CN): a clue to the control of granulopoiesis 总被引:2,自引:0,他引:2
A simple quantitative feedback model of granulopoiesis is presented and discussed within the framework of existing data on granulopoiesis in both normals and patients with cyclic neutropenia (CN). The model assumes that the controlled compartment is the bone marrow pool of mature neutrophils (PMNs), which sends a negative feedback signal to the mitotic pool of early granulocyte precursors (i.e., CFU-C, myeloblasts, etc.) thus controlling the granulocyte production rate. Three parameters are found to play important roles in determining the response of the system to perturbations. These are: TM, the granulocyte maturation time; a, a parameter reflecting the strength of the negative feedback exerted by mature PMNs on the granulocyte production rate; and b, a parameter describing the leakiness of the bone marrow for PMN egress. It is shown that depending on the relative magnitudes of a and b, the system will either respond to perturbations with a damped oscillation (a less than b: the normal state) or with a sustained oscillation (a greater than b: the CN state). In both cases, the oscillation period is found to approximately equal 2TM. Deductions of the values of a, b, and TM from experimental data are consistent with the predictions of the model and show an increased value of a in CN relative to the normal state. This suggests an overly active feedback mechanism as the pathophysiologic basis of CN. In addition, the model can explain how various therapeutic agent correct CN and also provides insight into why other hematologic cell lines and CSA oscillate in CN. 相似文献
28.
Weinberg JB; Misukonis MA; Shami PJ; Mason SN; Sauls DL; Dittman WA; Wood ER; Smith GK; McDonald B; Bachus KE 《Blood》1995,86(3):1184-1195
29.
Matthew GK Benesch Rongrong Wu Gopal Menon Kazuaki Takabe 《American journal of cancer research》2022,12(12):5403
Outcomes in pancreatic ductal adenocarcinoma (PDAC) are known to be worse in tumors with high integrin β1 expression, but targeted monotherapy against this integrin has not been effective. Seven other beta integrins are expressed in mammalian biology and they are known to have overlapping and compensatory signaling in biological systems. However, their roles in PDAC are poorly understood and have not been systematically compared to integrin β1 biology. In this study, we analyzed the clinical outcomes against beta integrin 1-8 (ITGB1-8) expression in PDAC samples from two large independent cohorts, The Cancer Genome Atlas (TCGA) and . Biological function and tumor microenvironment composition were studied using Gene Set Enrichment Analysis and xCell. Expression of all eight beta integrins is significantly increased in PDACs relative to normal pancreatic tissues (all P<0.001). ITGB1, 2, 5, and 6 have similarly enriched gene patterns related to transforming growth factor (TGF)-β, epithelial mesenchymal transition, inflammation, stemness, and angiogenesis pathways. Homologous recombination defects and neoantigens are increased in high-ITGB4, 5, and 6 tumors, with decreased overall survival in high-ITGB1, 5, and 6 tumors compared to low expression tumors (hazard ratios 1.5-2.0). High-ITGB1, 2, and 5 tumors have increased fibroblast infiltration (all P<0.01) while endothelial cells are increased in high-ITGB2 and 3 tumors (all P<0.05). Overall, beta integrin expression does not correlate to immune cell populations in PDACs. Therefore, while all beta integrins are overexpressed in PDACs, they exert differential effects on PDAC biology. ITGB2, 5, and 6 have a similar profile to ITGB1, suggesting that future research in PDAC integrin therapy needs to consider the complementary signaling profiles mediated by these integrins. GSE21501相似文献
30.