全文获取类型
收费全文 | 1006篇 |
免费 | 83篇 |
国内免费 | 1篇 |
专业分类
1090篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 21篇 |
2020年 | 9篇 |
2019年 | 14篇 |
2018年 | 16篇 |
2017年 | 24篇 |
2016年 | 38篇 |
2015年 | 63篇 |
2014年 | 73篇 |
2013年 | 78篇 |
2012年 | 87篇 |
2011年 | 76篇 |
2010年 | 60篇 |
2009年 | 45篇 |
2008年 | 59篇 |
2007年 | 62篇 |
2006年 | 61篇 |
2005年 | 37篇 |
2004年 | 39篇 |
2003年 | 43篇 |
2002年 | 39篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 8篇 |
1997年 | 12篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1974年 | 3篇 |
1973年 | 1篇 |
1971年 | 2篇 |
排序方式: 共有1090条查询结果,搜索用时 0 毫秒
61.
Wouter?T.?GudeEmail author Mari?tte?M.?van Engen-Verheul Sabine?N.?van der Veer Hareld?M.?C.?Kemps Monique?W.?M.?Jaspers Nicolette?F.?de Keizer Niels?Peek 《Implementation science : IS》2015,11(1):160
Background
The objective of this study was to assess the effect of a web-based audit and feedback (A&F) intervention with outreach visits to support decision-making by multidisciplinary teams.Methods
We performed a multicentre cluster-randomized trial within the field of comprehensive cardiac rehabilitation (CR) in the Netherlands. Our participants were multidisciplinary teams in Dutch CR centres who were enrolled in the study between July 2012 and December 2013 and received the intervention for at least 1 year. The intervention included web-based A&F with feedback on clinical performance, facilities for goal setting and action planning, and educational outreach visits. Teams were randomized either to receive feedback that was limited to psychosocial rehabilitation (study group A) or to physical rehabilitation (study group B). The main outcome measure was the difference in performance between study groups in 11 care processes and six patient outcomes, measured at patient level. Secondary outcomes included effects on guideline concordance for the four main CR therapies.Results
Data from 18 centres (14,847 patients) were analysed, of which 12 centres (9353 patients) were assigned to group A and six (5494 patients) to group B. During the intervention, a total of 233 quality improvement goals was identified by participating teams, of which 49 (21%) were achieved during the study period. Except for a modest improvement in data completeness (4.5% improvement per year; 95% CI 0.65 to 8.36), we found no effect of our intervention on any of our primary or secondary outcome measures.Conclusions
Within a multidisciplinary setting, our web-based A&F intervention engaged teams to define local performance improvement goals but failed to support them in actually completing the improvement actions that were needed to achieve those goals. Future research should focus on improving the actionability of feedback on clinical performance and on addressing the socio-technical perspective of the implementation process.Trial registration
NTR325162.
Freek?Cox Eirikur?SaelandEmail author Matthijs?Baart Martin?Koldijk Jeroen?Tolboom Liesbeth?Dekking Wouter?Koudstaal Karin?L?vgren Bengtsson Jaap?Goudsmit Katarina?Rado?evi? 《Virology journal》2015,12(1):210
Background
Influenza virus infections are responsible for significant morbidity worldwide and therefore it remains a high priority to develop more broadly protective vaccines. Adjuvation of current seasonal influenza vaccines has the potential to achieve this goal.Methods
To assess the immune potentiating properties of Matrix-M?, mice were immunized with virosomal trivalent seasonal vaccine adjuvated with Matrix-M?. Serum samples were isolated to determine the hemagglutination inhibiting (HAI) antibody titers against vaccine homologous and heterologous strains. Furthermore, we assess whether adjuvation with Matrix-M? broadens the protective efficacy of the virosomal trivalent seasonal vaccine against vaccine homologous and heterologous influenza viruses.Results
Matrix-M? adjuvation enhanced HAI antibody titers and protection against vaccine homologous strains. Interestingly, Matrix-M? adjuvation also resulted in HAI antibody titers against heterologous influenza B strains, but not against the tested influenza A strains. Even though the protection against heterologous influenza A was induced by the adjuvated vaccine, in the absence of HAI titers the protection was accompanied by severe clinical scores and body weight loss. In contrast, in the presence of heterologous HAI titers full protection against the heterologous influenza B strain without any disease symptoms was obtained.Conclusion
The results of this study emphasize the promising potential of a Matrix-M?-adjuvated seasonal trivalent virosomal influenza vaccine. Adjuvation of trivalent virosomal vaccine does not only enhance homologous protection, but in addition induces protection against heterologous strains and thus provides overall more potent and broad protective immunity.63.
Detailed imaging and genetic analysis reveal a secondary BRAFL505H resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib 下载免费PDF全文
Inge Ubink Nicolle J. M. Besselink Mark Pieterse Wouter Veldhuis Marijn van Stralen Eelco F. J. Meijer Stefan M. Willems Michael A. Hadders Thomas Kuilman Oscar Krijgsman Daniel S. Peeper Marco J. Koudijs Edwin Cuppen Emile E. Voest Martijn P. Lolkema 《Pigment cell & melanoma research》2015,28(3):318-323
Resistance to treatment is the main problem of targeted treatment for cancer. We followed ten patients during treatment with vemurafenib, by three‐dimensional imaging. In all patients, only a subset of lesions progressed. Next‐generation DNA sequencing was performed on sequential biopsies in four patients to uncover mechanisms of resistance. In two patients, we identified mutations that explained resistance to vemurafenib; one of these patients had a secondary BRAF L505H mutation. This is the first observation of a secondary BRAF mutation in a vemurafenib‐resistant patient‐derived melanoma sample, which confirms the potential importance of the BRAF L505H mutation in the development of therapy resistance. Moreover, this study hints toward an important role for tumor heterogeneity in determining the outcome of targeted treatments. 相似文献
64.
Anouk A. J. Hamers Laura van Dam José M. Teixeira Duarte Mariska Vos Goran Marinkovi? Claudia M. van Tiel Sybren L. Meijer Anne-Marieke van Stalborch Stephan Huveneers Anje A. te Velde Wouter J. de Jonge Carlie J. M. de Vries 《PloS one》2015,10(8)
Nuclear receptor Nur77, also referred to as NR4A1 or TR3, plays an important role in innate and adaptive immunity. Nur77 is crucial in regulating the T helper 1/regulatory T-cell balance, is expressed in macrophages and drives M2 macrophage polarization. In this study we aimed to define the function of Nur77 in inflammatory bowel disease. In wild-type and Nur77-/- mice, colitis development was studied in dextran sodium sulphate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced models. To understand the underlying mechanism, Nur77 was overexpressed in macrophages and gut epithelial cells. Nur77 protein is expressed in colon tissues from Crohn’s disease and Ulcerative colitis patients and colons from colitic mice in inflammatory cells and epithelium. In both mouse colitis models inflammation was increased in Nur77-/- mice. A higher neutrophil influx and enhanced IL-6, MCP-1 and KC production was observed in Nur77-deficient colons after DSS-treatment. TNBS-induced influx of T-cells and inflammatory monocytes into the colon was higher in Nur77-/- mice, along with increased expression of MCP-1, TNFα and IL-6, and decreased Foxp3 RNA expression, compared to wild-type mice. Overexpression of Nur77 in lipopolysaccharide activated RAW macrophages resulted in up-regulated IL-10 and downregulated TNFα, MIF-1 and MCP-1 mRNA expression through NFκB repression. Nur77 also strongly decreased expression of MCP-1, CXCL1, IL-8, MIP-1α and TNFα in gut epithelial Caco-2 cells. Nur77 overexpression suppresses the inflammatory status of both macrophages and gut epithelial cells and together with the in vivo mouse data this supports that Nur77 has a protective function in experimental colitis. These findings may have implications for development of novel targeted treatment strategies regarding inflammatory bowel disease and other inflammatory diseases. 相似文献
65.
Marsh K?nigs Wouter D. Weeda L. W. Ernest van Heurn R. Jeroen Vermeulen J. Carel Goslings Jan S. K. Luitse Bwee Tien Poll-Thé Anita Beelen Marleen van der Wees Rachèl J. J. K. Kemps Coriene E. Catsman-Berrevoets Jaap Oosterlaan 《PloS one》2015,10(12)
Background
Axonal injury after traumatic brain injury (TBI) may cause impaired sensory integration. We aim to determine the effects of childhood TBI on visual integration in relation to general neurocognitive functioning.Methods
We compared children aged 6–13 diagnosed with TBI (n = 103; M = 1.7 years post-injury) to children with traumatic control (TC) injury (n = 44). Three TBI severity groups were distinguished: mild TBI without risk factors for complicated TBI (mildRF- TBI, n = 22), mild TBI with ≥1 risk factor (mildRF+ TBI, n = 46) or moderate/severe TBI (n = 35). An experimental paradigm measured speed and accuracy of goal-directed behavior depending on: (1) visual identification; (2) visual localization; or (3) both, measuring visual integration. Group-differences on reaction time (RT) or accuracy were tracked down to task strategy, visual processing efficiency and extra-decisional processes (e.g. response execution) using diffusion model analysis. General neurocognitive functioning was measured by a Wechsler Intelligence Scale short form.Results
The TBI group had poorer accuracy of visual identification and visual integration than the TC group (Ps ≤ .03; ds ≤ -0.40). Analyses differentiating TBI severity revealed that visual identification accuracy was impaired in the moderate/severe TBI group (P = .05, d = -0.50) and that visual integration accuracy was impaired in the mildRF+ TBI group and moderate/severe TBI group (Ps < .02, ds ≤ -0.56). Diffusion model analyses tracked impaired visual integration accuracy down to lower visual integration efficiency in the mildRF+ TBI group and moderate/severe TBI group (Ps < .001, ds ≤ -0.73). Importantly, intelligence impairments observed in the TBI group (P = .009, d = -0.48) were statistically explained by visual integration efficiency (P = .002).Conclusions
Children with mildRF+ TBI or moderate/severe TBI have impaired visual integration efficiency, which may contribute to poorer general neurocognitive functioning. 相似文献66.
Yi Wu Noshir F. Dabhoiwala Jaco Hagoort Jin-Lu Shan Li-Wen Tan Bin-Ji Fang Shao-Xiang Zhang Wouter H. Lamers 《PloS one》2015,10(8)
Background
Pelvic-floor anatomy is usually studied by artifact-prone dissection or imaging, which requires prior anatomical knowledge. We used the serial-section approach to settle contentious issues and an interactive 3D-pdf to make the results widely accessible.Method
3D reconstructions of undeformed thin serial anatomical sections of 4 females and 2 males (21–35y) of the Chinese Visible Human database.Findings
Based on tendinous septa and muscle-fiber orientation as segmentation guides, the anal-sphincter complex (ASC) comprised the subcutaneous external anal sphincter (EAS) and the U-shaped puborectal muscle, a part of the levator ani muscle (LAM). The anococcygeal ligament fixed the EAS to the coccygeal bone. The puborectal-muscle loops, which define the levator hiatus, passed around the anorectal junction and inserted anteriorly on the perineal body and pubic bone. The LAM had a common anterior attachment to the pubic bone, but separated posteriorly into puborectal and “pubovisceral” muscles. This pubovisceral muscle was bilayered: its internal layer attached to the conjoint longitudinal muscle of the rectum and the rectococcygeal fascia, while its outer, patchy layer reinforced the inner layer. ASC contraction makes the ano-rectal bend more acute and lifts the pelvic floor. Extensions of the rectal longitudinal smooth muscle to the coccygeal bone (rectococcygeal muscle), perineal body (rectoperineal muscle), and endopelvic fascia (conjoint longitudinal and pubovisceral muscles) formed a “diaphragm” at the inferior boundary of the mesorectum that suspended the anorectal junction. Its contraction should straighten the anorectal bend.Conclusion
The serial-section approach settled contentious topographic issues of the pelvic floor. We propose that the ASC is involved in continence and the rectal diaphragm in defecation. 相似文献67.
Wouter Everaerts Bernd Nilius Grzegorz Owsianik 《Progress in biophysics and molecular biology》2010,103(1):2-17
The Transient Receptor Potential Vanilloid 4 channel, TRPV4, is a Ca2+ and Mg2+ permeable non-selective cation channel involved in many different cellular functions. It is activated by a variety of physical and chemical stimuli, including heat, mechano-stimuli, endogenous substances such as arachidonic acid and its cytochrome P450-derived metabolites (epoxyeicosatrienoic acids), endocannabinoids (anandamide and 2-arachidonoylglycerol), as well as synthetic α-phorbol derivatives. Recently, TRPV4 has been characterized as an important player modulating osteoclast differentiation in bone remodelling and as a urothelial mechanosensor that controls normal voiding. Several TRPV4 gain-of-function mutations are shown to cause autosomal-dominant bone dysplasias such as brachyolmia and Koszlowski disease. In this review we comprehensively describe the structural, biophysical and (patho)physiological properties of the TRPV4 channel and we summarize the current knowledge about the role of TRPV4 in the pathogenesis of several diseases. 相似文献
68.
Borgonie G Dierick M Houthoofd W Willems M Jacobs P Bert W 《The Biological bulletin》2010,219(3):268-276
Organisms living in extreme habitats require costly adaptations to cope with these conditions. Among the suggested potential benefits that trade off these costs is refuge from predation. To study these interactions in extreme environments, samples were taken in the cave Cueva de Villa Luz, Tabasco, Mexico, where more than 32 subterranean springs, some H(2)S rich, rise from the floor. Hydrogen sulfide gas plus oxygen is absorbed by freshwater, and oxidation forms concentrated sulfuric acid. Snottites, whitish hollow mucous tubes, hang from the ceiling of the cave. Fluid drops from these snottites were recorded as having pH values of 0-3. We report the discovery of a new species of nematode that thrives in the highly acidic environment of the snottite. Micro CT scan of snottites reveals a complex interaction between the acidic snottite, nematodes, and abundant nematode-eating mites. The nematode adaptation to low pH probably protects them against mite predation, for which nematodes are most likely the most important source of carbon in this sulfur-driven ecosystem. 相似文献
69.
Jessica AB van Nies Rute B Marques Stella Trompet Zuzana de Jong Fina AS Kurreeman Rene EM Toes J Wouter Jukema Tom WJ Huizinga Annette HM van der Helm-van Mil 《Arthritis research & therapy》2010,12(2):R38
Introduction
Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients. 相似文献70.
Marijn Rutgers Daniël BF Saris Wouter JA Dhert Laura B Creemers 《Arthritis research & therapy》2010,12(3):R114