全文获取类型
收费全文 | 4962篇 |
免费 | 401篇 |
出版年
2023年 | 37篇 |
2022年 | 69篇 |
2021年 | 123篇 |
2020年 | 71篇 |
2019年 | 82篇 |
2018年 | 125篇 |
2017年 | 86篇 |
2016年 | 155篇 |
2015年 | 251篇 |
2014年 | 252篇 |
2013年 | 340篇 |
2012年 | 387篇 |
2011年 | 355篇 |
2010年 | 245篇 |
2009年 | 224篇 |
2008年 | 307篇 |
2007年 | 324篇 |
2006年 | 270篇 |
2005年 | 236篇 |
2004年 | 239篇 |
2003年 | 221篇 |
2002年 | 160篇 |
2001年 | 49篇 |
2000年 | 50篇 |
1999年 | 58篇 |
1998年 | 59篇 |
1997年 | 36篇 |
1996年 | 33篇 |
1995年 | 35篇 |
1994年 | 27篇 |
1993年 | 22篇 |
1992年 | 31篇 |
1991年 | 33篇 |
1990年 | 28篇 |
1989年 | 24篇 |
1988年 | 12篇 |
1987年 | 16篇 |
1986年 | 15篇 |
1985年 | 25篇 |
1984年 | 28篇 |
1983年 | 20篇 |
1982年 | 21篇 |
1981年 | 18篇 |
1979年 | 15篇 |
1978年 | 10篇 |
1977年 | 14篇 |
1975年 | 9篇 |
1974年 | 14篇 |
1973年 | 12篇 |
1972年 | 10篇 |
排序方式: 共有5363条查询结果,搜索用时 15 毫秒
991.
André G?hler Adrian Hetzer Birte Holtfreter Marie Henrike Geisel Carsten Oliver Schmidt Ivo Steinmetz Thomas Kocher 《PloS one》2014,9(7)
Periodontitis is a multi-microbial oral infection with high prevalence among adults. Putative oral pathogens are commonly found in periodontally diseased individuals. However, these organisms can be also detected in the oral cavity of healthy subjects. This leads to the hypothesis, that alterations in the proportion of these organisms relative to the total amount of oral microorganisms, namely their abundance, rather than their simple presence might be important in the transition from health to disease. Therefore, we developed a quantitative molecular method to determine the abundance of various oral microorganisms and the portion of bacterial and archaeal nucleic acid relative to the total nucleic acid extracted from individual samples. We applied quantitative real-time PCRs targeting single-copy genes of periodontal bacteria and 16S-rRNA genes of Bacteria and Archaea. Testing tongue scrapings of 88 matched pairs of periodontally diseased and healthy subjects revealed a significantly higher abundance of P. gingivalis and a higher total bacterial abundance in diseased subjects. In fully adjusted models the risk of being periodontally diseased was significantly higher in subjects with high P. gingivalis and total bacterial abundance. Interestingly, we found that moderate abundances of A. actinomycetemcomitans were associated with reduced risk for periodontal disease compared to subjects with low abundances, whereas for high abundances, this protective effect leveled off. Moderate archaeal abundances were health associated compared to subjects with low abundances. In conclusion, our methodological approach unraveled associations of the oral flora with periodontal disease, which would have gone undetected if only qualitative data had been determined. 相似文献
992.
Melanie Calvert Derek Kyte Helen Duffy Adrian Gheorghe Rebecca Mercieca-Bebber Jonathan Ives Heather Draper Michael Brundage Jane Blazeby Madeleine King 《PloS one》2014,9(10)
Background
Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.Methods and Findings
We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.Conclusions
PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. 相似文献993.
The behavioural ecology of terrestrial molluscs is poorly known. We consider the behavioural ecology of three morphologically similar, parapatric camaenids of southeast Australia: Meridolum corneovirens, Meridolum middenense, and Pommerhelix duralensis. We critically review available literature on their behaviour and address knowledge gaps through field and laboratory studies, including spool-line tracking data for P. duralensis and M. corneovirens. These data are supplemented by in situ observation for each species and ex situ dietary preference studies for P. duralensis and M. corneovirens. Our results suggest a complex behavioural ecology for each species, with some inter-specific behavioural differences within the morphologically conservative group. Implications for invertebrate conservation planning are briefly discussed. 相似文献
994.
995.
Jacobo Elies Mark L. Dallas John P. Boyle Jason L. Scragg Adrian Duke Derek S. Steele Chris Peers 《The Journal of biological chemistry》2014,289(23):16421-16429
Sublethal carbon monoxide (CO) exposure is frequently associated with myocardial arrhythmias, and our recent studies have demonstrated that these may be attributable to modulation of cardiac Na+ channels, causing an increase in the late current and an inhibition of the peak current. Using a recombinant expression system, we demonstrate that CO inhibits peak human Nav1.5 current amplitude without activation of the late Na+ current observed in native tissue. Inhibition was associated with a hyperpolarizing shift in the steady-state inactivation properties of the channels and was unaffected by modification of channel gating induced by anemone toxin (rATX-II). Systematic pharmacological assessment indicated that no recognized CO-sensitive intracellular signaling pathways appeared to mediate CO inhibition of Nav1.5. Inhibition was, however, markedly suppressed by inhibition of NO formation, but NO donors did not mimic or occlude channel inhibition by CO, indicating that NO alone did not account for the actions of CO. Exposure of cells to DTT immediately before CO exposure also dramatically reduced the magnitude of current inhibition. Similarly, l-cysteine and N-ethylmaleimide significantly attenuated the inhibition caused by CO. In the presence of DTT and the NO inhibitor Nω-nitro-l-arginine methyl ester hydrochloride, the ability of CO to inhibit Nav1.5 was almost fully prevented. Our data indicate that inhibition of peak Na+ current (which can lead to Brugada syndrome-like arrhythmias) occurs via a mechanism distinct from induction of the late current, requires NO formation, and is dependent on channel redox state. 相似文献
996.
James R. R. Whittle Adam K. Wheatley Lan Wu Daniel Lingwood Masaru Kanekiyo Steven S. Ma Sandeep R. Narpala Hadi M. Yassine Gregory M. Frank Jonathan W. Yewdell Julie E. Ledgerwood Chih-Jen Wei Adrian B. McDermott Barney S. Graham Richard A. Koup Gary J. Nabel 《Journal of virology》2014,88(8):4047-4057
997.
Karen Ikin Philip S. Barton Emma Knight David B. Lindenmayer Joern Fischer Adrian D. Manning 《Oecologia》2014,174(2):545-557
New insights into community-level responses at the urban fringe, and the mechanisms underlying them, are needed. In our study, we investigated the compositional distinctiveness and variability of a breeding bird community at both sides of established edges between suburban residential areas and woodland reserves in Canberra, Australia. Our goals were to determine if: (1) community-level responses were direct (differed with distance from the edge, independent of vegetation) or indirect (differed in response to edge-related changes in vegetation), and (2) if guild-level responses provided the mechanism underpinning community-level responses. We found that suburbs and reserves supported significantly distinct bird communities. The suburban bird community, characterised by urban-adapted native and exotic species, had a weak direct edge response, with decreasing compositional variability with distance from the edge. In comparison, the reserve bird community, characterised by woodland-dependent species, was related to local tree and shrub cover. This was not an indirect response, however, as tree and shrub cover was not related to edge distance. We found that the relative richness of nesting, foraging and body size guilds also displayed similar edge responses, indicating that they underpinned the observed community-level responses. Our study illustrates how community-level responses provide valuable insights into how communities respond to differences in resources between two contrasting habitats. Further, the effects of the suburban matrix penetrate into reserves for greater distances than previously thought. Suburbs and adjacent reserves, however, provided important habitat resources for many native species and the conservation of these areas should not be discounted from continued management strategies. 相似文献
998.
A new horseshoe crab species, Limulus darwini, is described from the uppermost Jurassic (ca. 148 Ma) near-shore sediments of the Kcynia Formation, central Poland. The only extant species Limulus polyphemus (Linnaeus) inhabits brackish-marine, shallow water environments of the east coast of the United States. Here it is shown that there are no important morphological differences between the Kcynia Formation specimens and extant juvenile representatives of the genus Limulus. The palaeoecological setting inhabited by the new species and the trophic relationships of extant horseshoe crabs are discussed in an attempt to determine the potential range of food items ingested by these Mesozoic xiphosurans. In this paper we propose the adoption of a new term stabilomorphism, this being: an effect of a specific formula of adaptative strategy among organisms whose taxonomic status does not exceed genus-level. A high effectiveness of adaptation significantly reduces the need for differentiated phenotypic variants in response to environmental changes and provides for long-term evolutionary success. 相似文献
999.
Ruth Tevlin Adrian McArdle Charles K.F. Chan John Pluvinage Graham G. Walmsley Taylor Wearda Owen Marecic Michael S. Hu Kevin J. Paik Kshemendra Senarath-Yapa David A. Atashroo Elizabeth R. Zielins Derrick C. Wan Irving L. Weissman Michael T. Longaker 《Journal of visualized experiments : JoVE》2014,(93)
Osteoclasts are highly specialized cells that are derived from the monocyte/macrophage lineage of the bone marrow. Their unique ability to resorb both the organic and inorganic matrices of bone means that they play a key role in regulating skeletal remodeling. Together, osteoblasts and osteoclasts are responsible for the dynamic coupling process that involves both bone resorption and bone formation acting together to maintain the normal skeleton during health and disease.As the principal bone-resorbing cell in the body, changes in osteoclast differentiation or function can result in profound effects in the body. Diseases associated with altered osteoclast function can range in severity from lethal neonatal disease due to failure to form a marrow space for hematopoiesis, to more commonly observed pathologies such as osteoporosis, in which excessive osteoclastic bone resorption predisposes to fracture formation.An ability to isolate osteoclasts in high numbers in vitro has allowed for significant advances in the understanding of the bone remodeling cycle and has paved the way for the discovery of novel therapeutic strategies that combat these diseases. Here, we describe a protocol to isolate and cultivate osteoclasts from mouse bone marrow that will yield large numbers of osteoclasts. 相似文献
1000.