全文获取类型
收费全文 | 4620篇 |
免费 | 345篇 |
国内免费 | 1篇 |
出版年
2023年 | 33篇 |
2022年 | 83篇 |
2021年 | 130篇 |
2020年 | 81篇 |
2019年 | 126篇 |
2018年 | 167篇 |
2017年 | 142篇 |
2016年 | 175篇 |
2015年 | 236篇 |
2014年 | 249篇 |
2013年 | 347篇 |
2012年 | 344篇 |
2011年 | 367篇 |
2010年 | 250篇 |
2009年 | 213篇 |
2008年 | 216篇 |
2007年 | 224篇 |
2006年 | 162篇 |
2005年 | 153篇 |
2004年 | 128篇 |
2003年 | 114篇 |
2002年 | 102篇 |
2001年 | 85篇 |
2000年 | 108篇 |
1999年 | 75篇 |
1998年 | 56篇 |
1997年 | 28篇 |
1996年 | 31篇 |
1995年 | 26篇 |
1994年 | 13篇 |
1993年 | 17篇 |
1992年 | 21篇 |
1991年 | 19篇 |
1990年 | 14篇 |
1989年 | 25篇 |
1988年 | 15篇 |
1987年 | 15篇 |
1986年 | 21篇 |
1985年 | 15篇 |
1984年 | 26篇 |
1983年 | 23篇 |
1982年 | 23篇 |
1981年 | 14篇 |
1980年 | 34篇 |
1979年 | 28篇 |
1978年 | 27篇 |
1977年 | 25篇 |
1976年 | 13篇 |
1974年 | 12篇 |
1973年 | 12篇 |
排序方式: 共有4966条查询结果,搜索用时 31 毫秒
171.
Randa?Attieh Marie-Pierre?GagnonEmail author Carole?A?Estabrooks France?Légaré Mathieu?Ouimet Geneviève?Roch El?Kebir?Ghandour Jeremy?Grimshaw 《Implementation science : IS》2013,8(1):138
Background
With the persistent gaps between research and practice in healthcare systems, knowledge translation (KT) has gained significance and importance. Also, in most industrialized countries, there is an increasing emphasis on managing chronic health conditions with the best available evidence. Yet, organizations aiming to improve chronic care (CC) require an adequate level of organizational readiness (OR) for KT.Objectives: The purpose of this study is to review and synthesize the existing evidence on conceptual models/frameworks of Organizational Readiness for Change (ORC) in healthcare as the basis for the development of a comprehensive framework of OR for KT in the context of CC.Data sources
We conducted a systematic review of the literature on OR for KT in CC using Pubmed, Embase, CINAHL, PsychINFO, Web of Sciences (SCI and SSCI), and others. Search terms included readiness; commitment and change; preparedness; willing to change; organization and administration; and health and social services.Study selection: The search was limited to studies that had been published between the starting date of each bibliographic database (e.g., 1964 for PubMed) and November 1, 2012. Only papers that refer to a theory, a theoretical component from any framework or model on OR that were applicable to the healthcare domain were considered. We analyzed data using conceptual mapping.Data extraction: Pairs of authors independently screened the published literature by reviewing their titles and abstracts. Then, the two same reviewers appraised the full text of each study independently.Results
Overall, we found and synthesized 10 theories, theoretical models and conceptual frameworks relevant to ORC in healthcare described in 38 publications. We identified five core concepts, namely organizational dynamics, change process, innovation readiness, institutional readiness, and personal readiness. We extracted 17 dimensions and 59 sub-dimensions related to these 5 concepts.Conclusion
Our findings provide a useful overview for researchers interested in ORC and aims to create a consensus on the core theoretical components of ORC in general and of OR for KT in CC in particular. However, more work is needed to define and validate the core elements of a framework that could help to assess OR for KT in CC.172.
Soheir M. El Nahas Mona A. Bibars Dalia A. Taha Hassan I. El-Sayyad 《Journal of Genetic Engineering and Biotechnology》2013,11(1):75-77
The present study investigates CSN1S1 casein gene polymorphism in Egyptian buffalo. CSN1S1 was analyzed in 17 unrelated Egyptian lactating buffalo. The amplified segment includes the last 43 amino acids of Exon 17 and part of Intron 17. In the present study we report for the first time the presence of 2 variants 178Ser (TCA) and 178Leu (TTA) in Egyptian buffalo CSN1S1 gene. The genotypic frequencies in the investigated Egyptian buffalo sample were 0.47, 0.058 and 0.47 for homozygous 178Ser, for homozygous 178Leu and heterozygous 178Leu/Ser, respectively. The 178Ser and 178Leu variant frequencies are 0.64 and 0.36, respectively which indicates the superiority of variant 178Ser in Egyptian buffalo. The allelic frequency in Egyptian buffalo is not much different from the corresponding allelic frequency in Italian buffalo (0.69 and 0.31 for 178Ser and 178Leu, respectively) as reported by Chianese et al. [3]. This is not surprising since they both belong to Mediterranean type. 相似文献
173.
Rafael Luis Kessler Daniela Fiori Gradia Rita de Cássia Pontello Rampazzo édio Elígio Louren?o Nilson José Fidêncio Lauro Manhaes Christian Macagnan Probst Andréa Rodrigues ávila Stenio Perdig?o Fragoso 《PloS one》2013,8(6)
Trypanosoma cruzi is the etiological agent of Chagas disease, an illness that affects about 10 million people, mostly in South America, for which there is no effective treatment or vaccine. In this context, transgenic parasites expressing reporter genes are interesting tools for investigating parasite biology and host-parasite interactions, with a view to developing new strategies for disease prevention and treatment. We describe here the construction of a stably transfected fluorescent T. cruzi clone in which the GFP gene is integrated into the chromosome carrying the ribosomal cistron in T. cruzi Dm28c. This fluorescent T. cruzi produces detectable amounts of GFP only at replicative stages (epimastigote and amastigote), consistent with the larger amounts of GFP mRNA detected in these forms than in the non replicative trypomastigote stages. The fluorescence signal was also strongly correlated with the total number of parasites in T. cruzi cultures, providing a simple and rapid means of determining the growth inhibitory dose of anti-T.cruzi drugs in epimastigotes, by fluorometric microplate screening, and in amastigotes, by the flow cytometric quantification of T. cruzi-infected Vero cells. This fluorescent T. cruzi clone is, thus, an interesting tool for unbiased detection of the proliferating stages of the parasite, with multiple applications in the genetic analysis of T. cruzi, including analyses of host-parasite interactions, gene expression regulation and drug development. 相似文献
174.
Plants are redox systems and redox-active compounds control and regulate all aspects of their life. Recent studies have shown that changes in reactive oxygen species (ROS) concentration mediated by enzymatic and non-enzymatic antioxidants are transferred into redox signals used by plants to activate various physiological responses. An overview of the main antioxidants and redox signaling in plant cells is presented. In this review, the biological effects of ROS and related redox signals are discussed in the context of acclimation to changing environmental conditions. Special attention is paid to the role of thiol/disulfide exchange via thioredoxins (Trxs), glutaredoxins (Grxs) and peroxiredoxins (Prxs) in the redox regulatory network. In plants, chloroplasts and mitochondria occupying a chloroplasts and mitochondria play key roles in cellular metabolism as well as in redox regulation and signaling. The integrated redox functions of these organelles are discussed with emphasis on the importance of the chloroplast and mitochondrion to the nucleus retrograde signaling in acclimatory and stress response. 相似文献
175.
176.
177.
Kylie Kavanagh Mark A. Espeland Kim Sutton‐Tyrrell Emma Barinas‐Mitchell Samar R. El Khoudary Rachel P. Wildman 《Obesity (Silver Spring, Md.)》2013,21(5):1031-1038
Objective:
The liver is an insulin‐responsive organ that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormone binding globulin (SHBG). Our objective was to explore whether lower SHBG was associated with ectopic liver fat and mediated its effect on insulin resistance in The Study of Women's Health Across the Nation (SWAN).Design and Methods:
A subset of midlife African American and Caucasian women from SWAN (n = 208; 50.9 ± 0.18 yrs; 71% Caucasian) had computed tomography scans to quantify visceral, subcutaneous and liver fat. Blood samples were collected and assayed for hormonal and metabolic markers.Results:
The cohort, while overweight, was generally healthy, and both liver fat and SHBG were unaffected by menopausal stage or race. Both higher liver fat and lower SHBG levels were significantly associated with higher insulin concentrations after adjustment for adiposity (r = ?0.25, P < 0.001 and r = ?0.18, P = 0.01). SHBG and liver fat had additive effects on insulin concentrations such that women with the lowest SHBG and the highest fat levels had the highest values (interaction P = 0.09). The association between SHBG and insulin was more apparent among women with fattier livers. SHBG and liver fat appear to have independent effects on insulin levels as adjustment for each other did not diminish the strength of either association (P = 0.023 and 0.001 respectively).Conclusion:
These results confirmed the strong independent associations between increased liver fat and decreased SHBG with increased metabolic risk in midlife women. Further these data underscore the need for additional research into the role of liver fat in modifying SHBG's influence on insulin levels.178.
Epigenetic dysregulation in the developing Down syndrome cortex 总被引:1,自引:0,他引:1
Nady El Hajj Marcus Dittrich Julia Böck Theo F. J. Kraus Indrajit Nanda Tobias Müller 《Epigenetics》2016,11(8):563-578
179.
Garima Singhal ffolliott Martin Fisher Melissa J. Chee Tze Guan Tan Abdelfattah El Ouaamari Andrew C. Adams Robert Najarian Rohit N. Kulkarni Christophe Benoist Jeffrey S. Flier Eleftheria Maratos-Flier 《PloS one》2016,11(2)
Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue. In order to understand the physiology of FGF21 in the pancreas, we analyzed its expression and regulation in both acinar and islet tissues. We found that acinar tissue express 20-fold higher levels than that observed in islets. We also observed that pancreatic FGF21 is nutritionally regulated; a marked reduction in FGF21 expression was noted with fasting while obesity is associated with 3–4 fold higher expression. Acinar and islet cells are targets of FGF21, which when systemically administered, leads to phosphorylation of the downstream target ERK 1/2 in about half of acinar cells and a small subset of islet cells. Chronic, systemic FGF21 infusion down-regulates its own expression in the pancreas. Mice lacking FGF21 develop significant islet hyperplasia and periductal lymphocytic inflammation when fed with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased levels of inflammatory cells were coupled with elevated expression of cytokines such as TNFα, IFNγ and IL1β. We conclude that FGF21 acts to limit islet hyperplasia and may also prevent pancreatic inflammation. 相似文献
180.
Farah El Najjar Nicolás Cifuentes-Mu?oz Jing Chen Haining Zhu Ursula J. Buchholz Carole L. Moncman Rebecca Ellis Dutch 《PLoS pathogens》2016,12(9)
Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to-cell spread and provide insights into dissemination of respiratory viruses. 相似文献