全文获取类型
收费全文 | 1309篇 |
免费 | 78篇 |
出版年
2021年 | 7篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 11篇 |
2017年 | 11篇 |
2016年 | 20篇 |
2015年 | 28篇 |
2014年 | 45篇 |
2013年 | 81篇 |
2012年 | 97篇 |
2011年 | 81篇 |
2010年 | 57篇 |
2009年 | 61篇 |
2008年 | 78篇 |
2007年 | 79篇 |
2006年 | 72篇 |
2005年 | 74篇 |
2004年 | 76篇 |
2003年 | 74篇 |
2002年 | 82篇 |
2001年 | 8篇 |
2000年 | 12篇 |
1999年 | 18篇 |
1998年 | 25篇 |
1997年 | 15篇 |
1996年 | 19篇 |
1995年 | 14篇 |
1994年 | 15篇 |
1993年 | 13篇 |
1992年 | 18篇 |
1990年 | 11篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1985年 | 8篇 |
1984年 | 13篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 11篇 |
1978年 | 6篇 |
1977年 | 7篇 |
1976年 | 4篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1968年 | 4篇 |
1963年 | 5篇 |
1962年 | 4篇 |
排序方式: 共有1387条查询结果,搜索用时 15 毫秒
41.
Beate Wieseler Natalia Wolfram Natalie McGauran Michaela F. Kerekes Volker Verv?lgyi Petra Kohlepp Marloes Kamphuis Ulrich Grouven 《PLoS medicine》2013,10(10)
Background
Access to unpublished clinical study reports (CSRs) is currently being discussed as a means to allow unbiased evaluation of clinical research. The Institute for Quality and Efficiency in Health Care (IQWiG) routinely requests CSRs from manufacturers for its drug assessments.Our objective was to determine the information gain from CSRs compared to publicly available sources (journal publications and registry reports) for patient-relevant outcomes included in IQWiG health technology assessments (HTAs) of drugs.Methods and Findings
We used a sample of 101 trials with full CSRs received for 16 HTAs of drugs completed by IQWiG between 15 January 2006 and 14 February 2011, and analyzed the CSRs and the publicly available sources of these trials. For each document type we assessed the completeness of information on all patient-relevant outcomes included in the HTAs (benefit outcomes, e.g., mortality, symptoms, and health-related quality of life; harm outcomes, e.g., adverse events). We dichotomized the outcomes as “completely reported” or “incompletely reported.” For each document type, we calculated the proportion of outcomes with complete information per outcome category and overall.We analyzed 101 trials with CSRs; 86 had at least one publicly available source, 65 at least one journal publication, and 50 a registry report. The trials included 1,080 patient-relevant outcomes. The CSRs provided complete information on a considerably higher proportion of outcomes (86%) than the combined publicly available sources (39%). With the exception of health-related quality of life (57%), CSRs provided complete information on 78% to 100% of the various benefit outcomes (combined publicly available sources: 20% to 53%). CSRs also provided considerably more information on harms. The differences in completeness of information for patient-relevant outcomes between CSRs and journal publications or registry reports (or a combination of both) were statistically significant for all types of outcomes.The main limitation of our study is that our sample is not representative because only CSRs provided voluntarily by pharmaceutical companies upon request could be assessed. In addition, the sample covered only a limited number of therapeutic areas and was restricted to randomized controlled trials investigating drugs.Conclusions
In contrast to CSRs, publicly available sources provide insufficient information on patient-relevant outcomes of clinical trials. CSRs should therefore be made publicly available. Please see later in the article for the Editors'' Summary 相似文献42.
43.
The hitherto unknown larva of Rhyacophila ferox Graf, 2006, is described and discussed in the context of contemporary Rhyacophilidae keys. In addition, zoogeographical and ecological notes are included. 相似文献
44.
45.
Annitella apfelbecki is one of three Annitella species with distribution ranges restricted to the Balkan Peninsula. In this paper, we describe the hitherto unknown female of A. apfelbecki and give the most important morphological features to enable its identification and separation from the other Annitella females. Additionally, we provide new data on distribution and discuss zoogeography, life cycle and ecology of this species. 相似文献
46.
Wolfram Noodt 《Studies on Neotropical Fauna and Environment》2013,48(2):84-129
En el curso de las investigaciones sobre la fauna de las aguas subterráneas límnicas de la Argentina, se encontraron en pocas muestras una sorprendente cantidad de especies de crustáceos. Una de las especies (Leptobathynella richerti) fué descubierta poco antes en Paraguay y 3 especies (Parastygocaris goerssi, P. andina e Ingolfiella uspallatae) ya han sido publicadas por el autor. Aqui se describen, se ilustran y se discuten 2 especies del género Parabathynella, 1 Nitocrella y 12 Parastenocaris como nuevas para la ciencia. Se completa la descripción de Leptobathynella richerti. Por falta de material, otras 5 especies aún no se han podido determinar. Por consiguiente, la fauna de las aguas subterráneas neotropicales prueba ser abun‐dante y representada por mudias especies también en la Argentina. Un análisis biogeo‐gráfico del material aparecerá en otra oportunidad con relaciones más ámplias. Las investigaciones serán continuadas. 相似文献
47.
Wolfram R. Zückert 《Molecular microbiology》2013,89(2):207-211
As the Lyme disease spirochaete Borrelia burgdorferi shuttles back and forth between arthropod vector and vertebrate host, it encounters vastly different and hostile environments. Major mechanisms contributing to the success of this pathogen throughout this complex transmission cycle are phase and antigenic variation of abundant and serotype‐defining surface lipoproteins. These peripherally membrane‐anchored virulence factors mediate niche‐specific interactions with vector/host factors and protect the spirochaete from the perils of the mammalian immune response. In this issue of Molecular Microbiology, Tilly, Bestor and Rosa redefine the roles of two lipoproteins, OspC and VlsE, during mammalian infection. Using a variety of promoter fusions in combination with a sensitive in vivo ‘use it or lose it’ gene complementation assay, the authors demonstrate that proper sequential expression of OspC followed by VlsE indeed matters. A previously suggested general functional redundancy between these and other lipoproteins is shown to be limited and dependent on an immunodeficient experimental setting that is arguably of diminished ecological relevance. These data reinforce the notion that OspC plays a unique role during initial infection while the antigenically variant VlsE proteins allow for persistence in the mammalian host. 相似文献
48.
Florence Schaffner Naho Yokota Tatiana Carneiro-Lobo Maki Kitano Michael Schaffer G. Mark Anderson Barbara M. Mueller Charles T. Esmon Wolfram Ruf 《PloS one》2013,8(4)
Several markers identify cancer stem cell-like populations, but little is known about the functional roles of stem cell surface receptors in tumor progression. Here, we show that the endothelial protein C receptor (EPCR), a stem cell marker in hematopoietic, neuronal and epithelial cells, is crucial for breast cancer growth in the orthotopic microenvironment of the mammary gland. Mice with a hypomorphic allele of EPCR show reduced tumor growth in the PyMT-model of spontaneous breast cancer development and deletion of EPCR in established PyMT tumor cells significantly attenuates transplanted tumor take and growth. We find expansion of EPCR+ cancer stem cell-like populations in aggressive, mammary fat pad-enhanced human triple negative breast cancer cells. In this model, EPCR-expressing cells have markedly increased mammosphere- and tumor-cell initiating activity compared to another stable progenitor-like subpopulation present at comparable frequency. We show that receptor blocking antibodies to EPCR specifically attenuate in vivo tumor growth initiated by either EPCR+ cells or the heterogenous mixture of EPCR+ and EPCR- cells. Furthermore, we have identified tumor associated macrophages as a major source for recognized ligands of EPCR, suggesting a novel mechanism by which cancer stem cell-like populations are regulated by innate immune cells in the tumor microenvironment. 相似文献
49.
50.
T. Reed Miller Peter Berrill Paul Wolfram Ranran Wang Yookyung Kim Xinzhu Zheng Edgar G. Hertwich 《Journal of Industrial Ecology》2019,23(6):1410-1424
Each year businesses, governments, and homeowners in the United States invest around one fifth of gross domestic product into the creation of capital assets such as buildings, machinery, and software to enable production and consumption. Use of capital is typically included to some extent in environmental life cycle assessments of goods and services but is not incorporated into most environmentally extended input‐output (EEIO) models, including the US Environmental Protection Agency's USEEIO. Capital assets are typically created in years prior to their use, so a challenge lies in distributing the impacts of their creation over time. In this work, a highly detailed capital flow matrix approach is followed to distribute the use of fixed capital assets to consuming industries. Data from the US Bureau of Economic Analysis's Fixed Asset Accounts is merged with its Industry Accounts data by the creation of concordance tables. Public highways and streets are partially reallocated to industries operating vehicles. The resulting capital use matrix is later combined into a modified USEEIO. “Housing” is found to be the largest consumer of fixed assets, followed by general government, fossil fuel extraction, and financial industries involved in leasing. Construction, vehicles, and machinery are mostly used by industries in the form of fixed assets. The types of fixed assets used by industries are consistent with expectations: housing is dominated by structures, transport by equipment, and information industries by intellectual property products. 相似文献