全文获取类型
收费全文 | 167篇 |
免费 | 22篇 |
国内免费 | 21篇 |
专业分类
基础医学 | 17篇 |
口腔科学 | 1篇 |
临床医学 | 38篇 |
内科学 | 35篇 |
皮肤病学 | 1篇 |
神经病学 | 3篇 |
特种医学 | 8篇 |
外科学 | 4篇 |
综合类 | 29篇 |
预防医学 | 1篇 |
眼科学 | 3篇 |
药学 | 51篇 |
中国医学 | 2篇 |
肿瘤学 | 17篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 13篇 |
2016年 | 7篇 |
2015年 | 17篇 |
2014年 | 13篇 |
2013年 | 24篇 |
2012年 | 20篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 7篇 |
2008年 | 10篇 |
2007年 | 7篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2003年 | 4篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 15 毫秒
1.
指数富集的配基系统进化(SELEX)是一种从大容量寡核苷酸文库中经反复分离扩增步骤得到针对靶分子的高亲和力高特异性核酸配基—适配体的体外筛选技术。SELEX技术自1990年发展至今,已涌现出多种筛选模式和分离方法。筛选特异结合蛋白质的SELEX技术发展直接影响和指导了适配体在蛋白质功能调控方面的应用。文章综述了多种SELEX技术在筛选蛋白质方面的发展近况,适配体在蛋白质功能研究中的应用,筛选过程中关键性因素的确定及适配体的前后期修饰。 相似文献
2.
本文建立一种基于免疫印迹的核酸适配体高敏定量分析的检测方法,并探讨其在适配体药物靶向性研究中的应用价值。首先用聚丙烯酰胺凝胶电泳进行核酸适配体的分离,然后利用电转的方法将凝胶上的核酸适配体转移至PVDF膜上,先后孵育Rabbit Anti-Biotin和HRP-Streptavidin抗体,最后利用化学发光仪进行成像。结果显示核酸适配体可以通过该方法进行定量检测分析,且该方法检测灵敏度高,能够识别荧光染料法检测不到的浓度范围。此外,该方法只识别被生物素修饰的核酸适配体,特异性强。结果提示,核酸免疫印记法可以作为核酸适配体药物靶向性研究的一个定量检测手段。 相似文献
3.
《Journal of microencapsulation》2013,30(7):701-708
AbstractNovel aptamer-functionalized polyethylene glycol–polylactic acid (PEG–PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer’s disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients. 相似文献
4.
J. P. VAVALLE C. P. RUSCONI S. ZELENKOFSKE W. A. WARGIN J. H. ALEXANDER R. C. BECKER 《Journal of thrombosis and haemostasis》2012,10(7):1303-1311
Summary. Background: The REG2 anticoagulation system consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous control agent, anivamersen. Objectives: To assess the safety, tolerability and pharmacokinetic and pharmacodynamic responses of REG2. Patients/Methods: In this phase 1a study, 36 healthy volunteers were enrolled into five cohorts and given one dose of pegnivacogin. Cohorts 1 (n = 6) and 1A (n = 4) received 0.5 mg kg?1; cohort 2 (n = 6) received 1.0 mg kg?1; cohort 3 (n = 6) received 3.0 mg kg?1; and cohort 4 (n = 8) received 2.0 mg kg?1. In cohorts 1–3, two subjects were randomized to placebo. Cohort 4 subjects were subsequently randomized to single‐dose (n = 4) or multidose (n = 4) anivamersen. Results: The mean maximum observed concentrations of pegnivacogin in cohorts 1, 1A, 2 and 3 at median time were 5.16 μg mL?1 at 84 h, 5.19 μg mL?1 at 72 h, 9.32 μg mL?1 at 90 h, and 32.5 μg mL?1 at 84 h, respectively. The maximum relative activated partial thromboplastin time and time needed to achieve this were 1.18 at 2 days, 1.16 at 2 days, 1.27 at 3 days, and 1.85 at 2 days, respectively. The calculated mean half‐life and mean residence times of pegnivacogin were 6.12 days and 9.6 days, respectively. There was rapid reversal with intravenous anivamersen, although subsequent reaccumulation of pegnivacogin was observed. Conclusions: In our first‐in‐human study, REG2 was well tolerated and provided dose‐proportional anticoagulation for several days after a single subcutaneous dose, with complete, although transient, reversal by its control agent. This study demonstrates the first application of a subcutaneously administered aptamer, and represents a potential advance in aptamer therapeutics. 相似文献
5.
Gerónimo Fernández Ana Moraga María I. Cuartero Alicia García-Culebras Carolina Peña-Martínez Jesús M. Pradillo Macarena Hernández-Jiménez Silvia Sacristán M. Irene Ayuso Rafael Gonzalo-Gobernado David Fernández-López M. Elena Martín María A. Moro Victor M. González Ignacio Lizasoain 《Molecular therapy》2018,26(8):2047-2059
6.
7.
8.
Michael A. Harris Timothy R. Pearce Thomas Pengo Huihui Kuang Colleen Forster Efrosini Kokkoli 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(1):85-96
In this work we hypothesized that the chemokine fractalkine can serve as a cancer molecular target. We engineered aptamer micelles functionalized with an outer poly(ethylene glycol) (PEG) corona, and investigated the extent and efficacy of using them as a targeting tool against fractalkine-expressing colon adenocarcinoma cells. In vitro cell binding results showed that aptamer micelles bound and internalized to fractalkine-expressing cancer cells with the majority of the micelles found free in the cytoplasm. Minimal surface binding was observed by healthy cells. Even though partial PEGylation did not prevent serum adsorption, micelles were highly resistant to endonuclease and exonuclease degradation. In vivo biodistribution studies and confocal studies demonstrated that even though both aptamer and control micelles showed tumor accumulation, only the aptamer micelles internalized into fractalkine-expressing cancer cells, thus demonstrating the potential of the approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells. 相似文献
9.
病原菌是各种感染性疾病的病原体之一,传统细菌培养鉴定方法耗时、操作繁琐,急需开发新的检测方法。基于纳米材料构建的适配体传感器具有灵敏度高、特异性好、操作简便、价格低廉等优势,有望用于病原菌检测。本文介绍了适配体传感器常用的纳米材料的特性和优势,以及不同检测方法适配体传感器检测各种病原菌的研究进展。 相似文献
10.
Aws Almufleh Liyong Zhang Lisa M. Mielniczuk Ellamae Stadnick Ross A. Davies Qiujiang Du Katey Rayner Peter P. Liu Sharon Chih 《Clinical transplantation》2020,34(1):e13765
Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV1-2 (mild-moderate CAV), CAV3 (severe CAV), and CAV0 (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies. 相似文献