全文获取类型
收费全文 | 163篇 |
免费 | 14篇 |
国内免费 | 6篇 |
专业分类
儿科学 | 3篇 |
妇产科学 | 2篇 |
基础医学 | 26篇 |
口腔科学 | 2篇 |
临床医学 | 19篇 |
内科学 | 25篇 |
皮肤病学 | 3篇 |
神经病学 | 8篇 |
特种医学 | 4篇 |
外科学 | 14篇 |
综合类 | 24篇 |
预防医学 | 5篇 |
眼科学 | 3篇 |
药学 | 20篇 |
中国医学 | 1篇 |
肿瘤学 | 24篇 |
出版年
2023年 | 4篇 |
2022年 | 8篇 |
2021年 | 15篇 |
2020年 | 6篇 |
2019年 | 17篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 7篇 |
2013年 | 11篇 |
2012年 | 7篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 1篇 |
2004年 | 8篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1998年 | 3篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
排序方式: 共有183条查询结果,搜索用时 18 毫秒
61.
目的研究舒血宁对严重创伤病人外周血中CD4、CD8、CD152活性的影响,探讨CD4、CD8、CD152的活性变化在严重创伤转归、预后判断及干预治疗方面的意义。方法研究对象为我院2008年7月以来收治的严重创伤病人117例,对照组64例给予常规治疗,试验组53例加用舒血宁20 ml/d治疗。于3 d、7 d两个时间点上,采用S-P(链亲和素-过氧化物酶)一步法测定患者外周血中CD4、CD8的活性;应用酶联免疫吸附法和流式细胞仪检测外周血中CD152的表达水平。结果试验组较对照组患者的CD4细胞数明显增多(P〈0.01),CD8细胞数无明显变化(P〉0.05),CD4/CD8比值明显增加(P〈0.05或P〈0.01),T细胞表面CD152水平明显降低(P〈0.01)。结论舒血宁能够明显提高Th细胞分泌IL-2的能力,使CD4细胞增多,CD4/CD8比值增加,并在一定程度上降低T细胞表面CD152的表达。该研究在探讨严重创伤后的免疫功能紊乱的发生机制、临床治疗和预后判断方面有重要意义。 相似文献
62.
Glioblastoma (GBM) is the most common central nervous system tumor and the molecular mechanism driving its development is still largely unknown, limiting the treatment of this disease. In the present study, we explored the potential role of miR-152 in glioblastoma stem cells (GSCs) as well as the possible molecular mechanisms. Our results proved that miR-152 was down-regulated in human GSCs. Restoring the expression of miR-152 dramatically reduced the cell proliferation, cell migration and invasion as well as inducing apoptosis. Mechanistic investigations defined Krüppel-like factor 4 (KLF4) as a direct and functional downstream target of miR-152, which was involved in the miR-152-mediated tumor-suppressive effects in GSCs. Meanwhile, this process was coincided with the down-regulated LGALS3 that could be bound and promoted by KLF4, leading to attenuate the activation of MEK1/2 and PI3K signal pathways. Moreover, the in vivo study showed that miR-152 over-expression and KLF4 knockdown produced the smallest tumor volume and the longest survival in nude mice. Taken together, these results elucidated the function of miR-152 in GSCs progression and suggested a promising application of it in glioma treatment. 相似文献
63.
The aim of this study was to determine the toxicokinetics of inhaled 1,1-difluoroethane (HFC-152a) in humans. Healthy volunteers were exposed to 0, 200 or 1000 ppm 1,1-difluoroethane for 2 h at light exercise in an exposure chamber. Capillary blood, urine and exhaled air were sampled up to 22 h post-exposure and analyzed for 1,1-difluoroethane. Fluoride and other potential metabolites were analyzed in urine. Symptoms of irritation and central nervous system effects were rated and inflammatory markers were analyzed in blood. Within a few minutes of exposure to 200 and 1000 ppm, 1,1-difluoroethane increased rapidly in blood and reached average levels of 7.4 and 34.3 μM, respectively. The post-exposure decreases in blood were fast and parallel to those in exhaled air. The observed time courses in blood and breath agreed well with those obtained with the PBPK model. The PBPK simulations indicate a net uptake during exposure to 1000 ppm of 6.6 mmol (6.7%) which corresponds to the amount exhaled post-exposure. About 20 μmol excess fluoride (0.013% of inhaled 1,1-difluoroethane on a molar basis) was excreted in urine after exposure to 1000 ppm, compared to control. No fluorine-containing metabolites were detected in urine. Symptom ratings and changes in inflammatory markers revealed no exposure-related effects. 相似文献
64.
Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 (IC50<0.5 μM), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 (IC50>20 μM). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at G0/G1 with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance. 相似文献
65.
RM Andrade J Hygino TM Kasahara MM Vieira LF Xavier B Blanco PV Damasco RM Silva DB Lima AL Oliveira AS Lemos AF Andrade CA Bento 《Clinical immunology (Orlando, Fla.)》2012,145(1):31-43
This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4(+)FoxP3(+)CD25(+)Treg cells in this patient group, high frequencies of IL-10-producing CD4(+)FoxP3(-) T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4(+)FoxP3(-)CD152(+) T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1β by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals. 相似文献
66.
Effects of miR-152 on Cell Growth Inhibition,Motility Suppression and Apoptosis Induction in Hepatocellular Carcinoma Cells
下载免费PDF全文
![点击此处可从《Asian Pacific journal of cancer prevention》网站下载免费的PDF全文](/ch/ext_images/free.gif)
《Asian Pacific journal of cancer prevention》2014,15(12):4969-4976
Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity,apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy. 相似文献
67.
目的:分析前列腺癌患者血清miR-146a与miR-152的表达水平及临床意义。方法:以2009年1月至2013年4月在我院泌尿外科诊治的前列腺癌、良性前列腺增生患者及健康体检志愿者各46例为研究对象,分析各组患者血清miR-146a与miR-152的表达水平及与临床病理参数之间的关系。结果:miR-146a在前列腺癌患者血清中的表达水平显著高于良性前列腺增生及正常组血清,且前列腺良性增生组血清中miR-146a的表达量亦较正常组高,差异均具有统计学意义(P0.05);miR-152在前列腺癌患者较良性前列腺增生及正常组血清显著偏低(P0.05),但在良性前列腺增生和正常组之间无统计学差异(P0.05);血清miR-146a在不同病理分期、临床分期、有无骨转移及血清t PSA有关(P0.05),与年龄无关(P0.05);而miR-152与不同病理分期、临床分期、有无骨转移有关(P0.05),与血清t PSA水平无相关性(P0.05),与年龄无显著相关性(P0.05)。结论:miR-146a与miR-152在前列腺癌患者血清中的表达水平发生了显著改变,为用于前列腺癌的早期诊断及病程的判断提供了相关实验依据。 相似文献
68.
Jinhwan Park Joohyun Kim Hwa Lee Minsoo Park Sehyun Baek 《Canadian journal of ophthalmology. Journal canadien d'ophtalmologie》2018,53(4):373-379
Objective
The purpose of this study was to evaluate the structure and function of the meibomian gland and the incomplete blinking rate to understand the pathophysiology of dry eye in thyroid eye disease (TED) patients.Methods
Patients who were diagnosed with TED were enrolled between October 2015 and February 2016. Clinical measurements were performed in the following order: (i) external examination (Hertel exophthalmometer and palpebral fissure height), (ii) LipiView interferometer (lipid layer thickness [LLT], incomplete blinking rate, and meibography), (iii) slit-lamp biomicroscopy (corneal surface staining, tear breakup time, meibum expression, Marx line).Results
Thirty eyes of 30 TED patients (male = 8; female = 22) were included in this study. The TED patient population had a mean age of 42.9 ± 11.8 years and a mean clinical activity score (CAS) of 2.33 ± 1.60. The meiboscore was 1.17 ± 0.90 in the upper eyelid and 0.70 ± 0.65 in the lower eyelid; scores were significantly higher in the upper eyelid (p < 0.001). The mean LLT was 82.43 ± 24.52 nm, and the mean incomplete blinking rate was 51.04 ± 33.62% (0–100%). CAS was the only variable that correlated with the meiboscore. There was no significant correlation between incomplete blinking and a degree of palpebral fissure height or proptosis.Conclusions
Tear film instability due to increased incomplete blinking can cause dry eye in TED. In addition to the increase in CAS, meibomian gland dysfunction may also be a cause of dry eye in TED. However, further comparative studies are needed to confirm these results. 相似文献69.
The inhalation of the following three propellants was tested in mice: trichlorofluoromethane (Fluorocarbon 11, FC11), dichlorofluoromethane (Fluorocarbon 12, FC12) and difluoroethane (Fluorocarbon 152a FC152a). There was a uniformity in nature of response of respiration and bronchopulmonary function, namely: reduction in respiratory rate, tidal volume and respiratory minute volume, decrease in pulmonary compliance and increase in pulmonary resistance. The differences between the three propellants were that FC11 caused spontaneous cardiac arrhythmias and sensitized the heart, whereas FC12 and FC152a did not. However, inhalation of FC152a caused sensitization of the heart to epinephrine in mice that had experimental bronchopulmonary lesions following intratracheal injection of papain. The bronchopulmonary system was influenced by inhalation of 1 to 2% concentration of the propellants, respiration by 2.5 to 5%, and the heart by 10 to 40%. 相似文献
70.
The inhalation of trichlorofluoromethane (FC11), dichlorotetrafluoroethane (FC114) and dichlorodifluoromethane (FC12) caused a reduction in mean aortic blood pressure but only FC11 and FC114 caused a reduction in mean pulmonary arterial pressure. The primary cause of the fall is a decrease in pulmonary blood flow. When blood flow to a lobe is kept constant and the adrenergic alpha receptors are blocked by injection of phentolamine, the inhalation of FC11 caused vasodilation. In the intact circulation, the vasodilation is masked by release of catecholamines which constrict the pulmonary blood vessels. 相似文献