全文获取类型
收费全文 | 91篇 |
免费 | 7篇 |
专业分类
98篇 |
出版年
2023年 | 2篇 |
2021年 | 3篇 |
2019年 | 4篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 5篇 |
2011年 | 9篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 5篇 |
2007年 | 5篇 |
2006年 | 1篇 |
2005年 | 1篇 |
2004年 | 3篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1986年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有98条查询结果,搜索用时 15 毫秒
1.
2.
Objective
In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry.Materials and Methods
We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry.Results
The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication.Discussion
Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased.Conclusion
Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. 相似文献3.
4.
Emma Bj?rkenstam Jurgita Narusyte Kristina Alexanderson Annina Ropponen Linnea Kjeldg?rd Pia Svedberg 《PloS one》2014,9(7)
Background
As the literature on long-term effects of childbirth on risk of morbidity or permanent work incapacity (DP) is limited, we aimed to study associations of childbirth with hospitalization and DP, adjusting for familial factors.Methods
This cohort study included female twins, i.e. women with twin sister, born 1959–1990 in Sweden (n = 5 118). At least one in the twin pair had their first childbirth 1994–2009. Women were followed regarding all-cause and cause-specific (mental or musculoskeletal diagnoses) DP during year 2–5 after first delivery or equivalent. Associations between childbirth, hospitalization and DP were calculated as hazard ratios (HR) with 95% confidence intervals (CI).Results
Women who did not give birth had markedly higher number of DP days/year compared to those giving birth. Hospitalization after first childbirth was associated with a higher HR of DP. Those hospitalized at least once after their first childbirth had a three-fold DP risk (HR: 3.2; 95% CI 1.1–9.6), DP due to mental diagnoses (HR: 3.2; 1.2–8.8), and of DP due to musculoskeletal diagnoses (HR: 6.1; 1.6–22.9). Lower HRs in the discordant twin pair analyses indicated that familial factors may influence the studied associations.Conclusions
Women who did not give birth had a much higher risk for DP than those who did. Among those who gave birth, the risk for DP was markedly higher among those with a previous hospitalization, and especially in women with repeated hospitalizations. The results indicate a health selection into giving birth as well as the importance of morbidity for DP. 相似文献5.
6.
Deanna Wolfson Michael Steck Martin Persson Gregory McNerney Ana Popovich Mattias Goksör Thomas Huser 《Journal of biophotonics》2015,8(3):208-216
We demonstrate an approach to rapidly characterize living suspension cells in 4 dimensions while they are immobilized and manipulated within optical traps. A single, high numerical aperture objective lens is used to separate the imaging plane from the trapping plane. This facilitates full control over the position and orientation of multiple trapped cells using a spatial light modulator, including directed motion and object rotation, while also allowing rapid 4D imaging. This system is particularly useful in the handling and investigation of the behavior of non‐adherent immune cells. We demonstrate these capabilities by imaging and manipulating living, fluorescently stained Jurkat T cells. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim) 相似文献
7.
Annina Kelloniemi Zoltan Szabo Raisa Serpi Juha N?p?nkangas Pauli Ohukainen Olli Tenhunen Leena Kaikkonen Elina Koivisto Zsolt Bagyura Risto Kerkel? Margret Leosdottir Thomas Hedner Olle Melander Heikki Ruskoaho Jaana Rys? 《PloS one》2015,10(6)
The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks’ follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio. 相似文献
8.
Roohparvar R Huser A Zwiers LH De Waard MA 《Applied and environmental microbiology》2007,73(15):5011-5019
Medical drugs known to modulate the activity of human ATP-binding cassette (ABC) transporter proteins (modulators) were tested for the ability to potentiate the activity of the azole fungicide cyproconazole against in vitro growth of Mycosphaerella graminicola and to control disease development due to this pathogen on wheat seedlings. In vitro modulation of cyproconazole activity could be demonstrated in paper disk bioassays. Some of the active modulators (amitriptyline, flavanone, and phenothiazines) increased the accumulation of cyproconazole in M. graminicola, suggesting that they reversed cyproconazole efflux. However, synergism between cyproconazole and modulators against M. graminicola on wheat seedlings could not be shown. Despite their low in vitro toxicity to M. graminicola, some modulators (amitriptyline, loperamide, and promazine) did show significant intrinsic disease control activity in preventive and curative foliar spray tests with wheat seedlings. The results suggest that these compounds have indirect disease control activity based on modulation of fungal ABC transporters essential for virulence and constitute a new class of disease control agents. 相似文献
9.
Dale BM McNerney GP Thompson DL Hubner W de Los Reyes K Chuang FY Huser T Chen BK 《Cell host & microbe》2011,10(6):551-562
HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both maturation and viral membrane fusion. Following VS transfer, viral membrane fusion occurs with delayed kinetics and transferred virions display reduced sensitivity to patient antisera compared to mature, cell-free virus. Furthermore, particle fusion requires that the transferred virions undergo proteolytic maturation within acceptor cell endosomes, which occurs over several hours. Rapid, live cell confocal microscopy demonstrated that viral fusion can occur in compartments that have moved away from the VS. Thus, HIV particle maturation activates viral fusion in target CD4+ T cell endosomes following transfer across the VS and may represent a pathway by which HIV evades antibody neutralization. 相似文献
10.
Dmitri Svistounov Alessandra Warren Gregory P. McNerney Dylan M. Owen Dusan Zencak Svetlana N. Zykova Harry Crane Thomas Huser Ronald J. Quinn B?rd Smedsr?d David G. Le Couteur Victoria C. Cogger 《PloS one》2012,7(9)
Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished. 相似文献