首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   5512篇
  免费   525篇
  国内免费   5篇
  2023年   29篇
  2022年   18篇
  2021年   131篇
  2020年   87篇
  2019年   108篇
  2018年   148篇
  2017年   119篇
  2016年   214篇
  2015年   292篇
  2014年   343篇
  2013年   372篇
  2012年   515篇
  2011年   509篇
  2010年   299篇
  2009年   263篇
  2008年   363篇
  2007年   359篇
  2006年   326篇
  2005年   258篇
  2004年   277篇
  2003年   217篇
  2002年   238篇
  2001年   58篇
  2000年   54篇
  1999年   45篇
  1998年   59篇
  1997年   33篇
  1996年   23篇
  1995年   29篇
  1994年   24篇
  1993年   17篇
  1992年   24篇
  1991年   20篇
  1990年   20篇
  1989年   17篇
  1988年   10篇
  1987年   11篇
  1986年   10篇
  1985年   15篇
  1984年   19篇
  1983年   5篇
  1982年   12篇
  1981年   10篇
  1980年   7篇
  1979年   9篇
  1978年   5篇
  1977年   3篇
  1974年   4篇
  1971年   4篇
  1968年   2篇
排序方式: 共有6042条查询结果,搜索用时 15 毫秒
61.

Background

Recent reviews have synthesised the psychometric properties of measures developed to examine implementation science constructs in healthcare and mental health settings. However, no reviews have focussed primarily on the properties of measures developed to assess innovations in public health and community settings. This review identified quantitative measures developed in public health and community settings, examined their psychometric properties, and described how the domains of each measure align with the five domains and 37 constructs of the Consolidated Framework for Implementation Research (CFIR).

Methods

MEDLINE, PsycINFO, EMBASE, and CINAHL were searched to identify publications describing the development of measures to assess implementation science constructs in public health and community settings. The psychometric properties of each measure were assessed against recommended criteria for validity (face/content, construct, criterion), reliability (internal consistency, test-retest), responsiveness, acceptability, feasibility, and revalidation and cross-cultural adaptation. Relevant domains were mapped against implementation constructs defined by the CFIR.

Results

Fifty-one measures met the inclusion criteria. The majority of these were developed in schools, universities, or colleges and other workplaces or organisations. Overall, most measures did not adequately assess or report psychometric properties. Forty-six percent of measures using exploratory factor analysis reported >50 % of variance was explained by the final model; none of the measures assessed using confirmatory factor analysis reported root mean square error of approximation (<0.06) or comparative fit index (>0.95). Fifty percent of measures reported Cronbach’s alpha of <0.70 for at least one domain; 6 % adequately assessed test-retest reliability; 16 % of measures adequately assessed criterion validity (i.e. known-groups); 2 % adequately assessed convergent validity (r?>?0.40). Twenty-five percent of measures reported revalidation or cross-cultural validation. The CFIR constructs most frequently assessed by the included measures were relative advantage, available resources, knowledge and beliefs, complexity, implementation climate, and other personal resources (assessed by more than ten measures). Five CFIR constructs were not addressed by any measure.

Conclusions

This review highlights gaps in the range of implementation constructs that are assessed by existing measures developed for use in public health and community settings. Moreover, measures with robust psychometric properties are lacking. Without rigorous tools, the factors associated with the successful implementation of innovations in these settings will remain unknown
  相似文献   
62.
Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81%) and bone formation (−80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.KEY WORDS: Whole-body vibration, LMHFV, Fracture healing, Oestrogen receptor signalling, Wnt signalling  相似文献   
63.
64.
Ulceration of primary melanomas is associated with poor prognosis yet is reported to predict benefit from adjuvant interferon. To better understand the biological processes involved, clinicopathological factors associated with ulceration were determined in 1804 patients. From this cohort, 348 primary tumor blocks were sampled to generate gene expression data using a 502‐gene cancer panel and 195 blocks were used for immunohistochemistry to detect macrophage infiltration and vessel density. Gene expression results were validated using a whole genome array in two independent sample sets. Ulceration of primary melanomas was associated with more proliferative tumors, tumor vessel invasion, and increased microvessel density. Infiltration of tumors with greater number of macrophages and gene expression pathways associated with wound healing and up‐regulation of pro‐inflammatory cytokines suggests that ulceration is associated with tumor‐related inflammation. The relative benefit from interferon reported in patients with ulcerated tumors may reflect modification of signaling pathways involved in inflammation.  相似文献   
65.
Conversion of native prairie to agriculture has increased food and bioenergy production but decreased wildlife habitat. However, enrollment of highly erodible cropland in conservation programs has compensated for some grassland loss. In the future, climate change and production of second-generation perennial biofuel crops could further transform agricultural landscapes and increase or decrease grassland area. Switchgrass (Panicum virgatum) is an alternative biofuel feedstock that may be economically and environmentally superior to maize (Zea mays) grain for ethanol production on marginally productive lands. Switchgrass could benefit farmers economically and increase grassland area, but there is uncertainty as to how conversions between rowcrops, switchgrass monocultures and conservation grasslands might occur and affect wildlife. To explore potential impacts on grassland birds, we developed four agricultural land-use change scenarios for an intensively cultivated landscape, each driven by potential future climatic changes and ensuing irrigation limitations, ethanol demand, commodity prices, and continuation of a conservation program. For each scenario, we calculated changes in area for landcover classes and predicted changes in grassland bird abundances. Overall, birds responded positively to the replacement of rowcrops with switchgrass and negatively to the conversion of conservation grasslands to switchgrass or rowcrops. Landscape context and interactions between climate, crop water use, and irrigation availability could influence future land-use, and subsequently, avian habitat quality and quantity. Switchgrass is likely to provide higher quality avian habitat than rowcrops but lower quality habitat than conservation grasslands, and therefore, may most benefit birds in heavily cultivated, irrigation dependent landscapes under warmer and drier conditions, where economic profitability may also encourage conversions to drought tolerant bioenergy feedstocks.  相似文献   
66.
The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies.  相似文献   
67.
68.
We inferred the population densities of blue whales (Balaenoptera musculus) and short-beaked common dolphins (Delphinus delphis) in the Northeast Pacific Ocean as functions of the water-column’s physical structure by implementing hierarchical models in a Bayesian framework. This approach allowed us to propagate the uncertainty of the field observations into the inference of species-habitat relationships and to generate spatially explicit population density predictions with reduced effects of sampling heterogeneity. Our hypothesis was that the large-scale spatial distributions of these two cetacean species respond primarily to ecological processes resulting from shoaling and outcropping of the pycnocline in regions of wind-forced upwelling and eddy-like circulation. Physically, these processes affect the thermodynamic balance of the water column, decreasing its volume and thus the height of the absolute dynamic topography (ADT). Biologically, they lead to elevated primary productivity and persistent aggregation of low-trophic-level prey. Unlike other remotely sensed variables, ADT provides information about the structure of the entire water column and it is also routinely measured at high spatial-temporal resolution by satellite altimeters with uniform global coverage. Our models provide spatially explicit population density predictions for both species, even in areas where the pycnocline shoals but does not outcrop (e.g. the Costa Rica Dome and the North Equatorial Countercurrent thermocline ridge). Interannual variations in distribution during El Niño anomalies suggest that the population density of both species decreases dramatically in the Equatorial Cold Tongue and the Costa Rica Dome, and that their distributions retract to particular areas that remain productive, such as the more oceanic waters in the central California Current System, the northern Gulf of California, the North Equatorial Countercurrent thermocline ridge, and the more southern portion of the Humboldt Current System. We posit that such reductions in available foraging habitats during climatic disturbances could incur high energetic costs on these populations, ultimately affecting individual fitness and survival.  相似文献   
69.
70.
BackgroundCirculating cell-free fetal DNA has enabled non-invasive prenatal fetal aneuploidy testing without direct discrimination of the maternal and fetal DNA. Testing may be improved by specifically enriching the sample material for fetal DNA. DNA methylation may allow for such a separation of DNA; however, this depends on knowledge of the methylomes of circulating cell-free DNA and its cellular contributors.ResultsWe perform whole genome bisulfite sequencing on a set of unmatched samples including circulating cell-free DNA from non-pregnant and pregnant female donors and genomic DNA from maternal buffy coat and placenta samples. We find CpG cytosines within longer fragments are more likely to be methylated. Comparison of the methylomes of placenta and non-pregnant circulating cell-free DNA reveal many of the 51,259 identified differentially methylated regions are located in domains exhibiting consistent placenta hypomethylation across millions of consecutive bases. We find these placenta hypomethylated domains are consistently located within regions exhibiting low CpG and gene density. Differentially methylated regions identified when comparing placenta to non-pregnant circulating cell-free DNA are recapitulated in pregnant circulating cell-free DNA, confirming the ability to detect differential methylation in circulating cell-free DNA mixtures.ConclusionsWe generate methylome maps for four sample types at single-base resolution, identify a link between DNA methylation and fragment length in circulating cell-free DNA, identify differentially methylated regions between sample groups, and uncover the presence of megabase-size placenta hypomethylated domains.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-015-0645-x) contains supplementary material, which is available to authorized users.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号