全文获取类型
收费全文 | 4145篇 |
免费 | 332篇 |
国内免费 | 2篇 |
专业分类
4479篇 |
出版年
2023年 | 24篇 |
2022年 | 60篇 |
2021年 | 109篇 |
2020年 | 56篇 |
2019年 | 75篇 |
2018年 | 116篇 |
2017年 | 85篇 |
2016年 | 151篇 |
2015年 | 199篇 |
2014年 | 246篇 |
2013年 | 323篇 |
2012年 | 391篇 |
2011年 | 335篇 |
2010年 | 223篇 |
2009年 | 181篇 |
2008年 | 242篇 |
2007年 | 212篇 |
2006年 | 194篇 |
2005年 | 186篇 |
2004年 | 171篇 |
2003年 | 149篇 |
2002年 | 138篇 |
2001年 | 26篇 |
2000年 | 27篇 |
1999年 | 34篇 |
1998年 | 45篇 |
1997年 | 17篇 |
1996年 | 22篇 |
1995年 | 18篇 |
1994年 | 21篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 15篇 |
1987年 | 16篇 |
1985年 | 11篇 |
1984年 | 25篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 18篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1977年 | 8篇 |
1974年 | 8篇 |
1973年 | 8篇 |
1964年 | 7篇 |
1962年 | 7篇 |
排序方式: 共有4479条查询结果,搜索用时 15 毫秒
81.
Atle van Beelen Granlund Arnar Flatberg Ann E. ?stvik Ignat Drozdov Bj?rn I. Gustafsson Mark Kidd Vidar Beisvag Sverre H. Torp Helge L. Waldum Tom Christian Martinsen Jan Kristian Dam?s Terje Espevik Arne K. Sandvik 《PloS one》2013,8(2)
Background
In inflammatory bowel disease (IBD), genetic susceptibility together with environmental factors disturbs gut homeostasis producing chronic inflammation. The two main IBD subtypes are Ulcerative colitis (UC) and Crohn’s disease (CD). We present the to-date largest microarray gene expression study on IBD encompassing both inflamed and un-inflamed colonic tissue. A meta-analysis including all available, comparable data was used to explore important aspects of IBD inflammation, thereby validating consistent gene expression patterns.Methods
Colon pinch biopsies from IBD patients were analysed using Illumina whole genome gene expression technology. Differential expression (DE) was identified using LIMMA linear model in the R statistical computing environment. Results were enriched for gene ontology (GO) categories. Sets of genes encoding antimicrobial proteins (AMP) and proteins involved in T helper (Th) cell differentiation were used in the interpretation of the results. All available data sets were analysed using the same methods, and results were compared on a global and focused level as t-scores.Results
Gene expression in inflamed mucosa from UC and CD are remarkably similar. The meta-analysis confirmed this. The patterns of AMP and Th cell-related gene expression were also very similar, except for IL23A which was consistently higher expressed in UC than in CD. Un-inflamed tissue from patients demonstrated minimal differences from healthy controls.Conclusions
There is no difference in the Th subgroup involvement between UC and CD. Th1/Th17 related expression, with little Th2 differentiation, dominated both diseases. The different IL23A expression between UC and CD suggests an IBD subtype specific role. AMPs, previously little studied, are strongly overexpressed in IBD. The presented meta-analysis provides a sound background for further research on IBD pathobiology. 相似文献82.
Wanda M. Admiraal Everlina M. Vlaar Vera Nierkens Frits Holleman Barend J. C. Middelkoop Karien Stronks Irene G. M. van Valkengoed 《PloS one》2013,8(7)
Aim
To study 1-year effectiveness of an intensive, culturally targeted lifestyle intervention in general practice for weight status and metabolic profile of South-Asians at risk of type 2 diabetes.Methods
536 South-Asians at risk of type 2 diabetes were randomized to an intervention (n = 283) or control (n = 253) group. The intervention, which was targeted culturally to the South-Asian population, consisted of individual lifestyle counselling, a family session, cooking classes, and supervised physical activity programme. All components of the intervention were carried out by professionals as part of their daily clinical practice. The control group received generic lifestyle advice. Change in weight status and metabolic profile were assessed after 1 year.Results
After 1 year, 201 participants were lost to follow-up. Remaining participants in intervention (n = 177) and control (n = 158) group had similar baseline characteristics. Weight loss in the intervention group was 0.2±3.3 kg, weight gain in the control group was 0.4±3.1 kg (p = 0.08). Changes in other weight-related measurements did not differ significantly between groups. Furthermore, there were no differences between groups in changes of metabolic profile. All results remained similar after repeating analyses in a multiple imputed dataset.Discussion
An intensive, culturally targeted, lifestyle intervention of 1 year did not improve weight status and metabolic profile of South-Asians at risk of type 2 diabetes. The laborious recruitment, high drop-out, and lack of effectiveness emphasise the difficulty of realising health benefits in practice and suggest that this strategy might not be the optimal approach for this population.Trial Registration
Nederlands Trial Register NTR1499 相似文献83.
Martine Stead Crawford Moodie Kathryn Angus Linda Bauld Ann McNeill James Thomas Gerard Hastings Kate Hinds Alison O'Mara-Eves Irene Kwan Richard I. Purves Stuart L. Bryce 《PloS one》2013,8(10)
Background and Objectives
Standardised or ‘plain’ tobacco packaging was introduced in Australia in December 2012 and is currently being considered in other countries. The primary objective of this systematic review was to locate, assess and synthesise published and grey literature relating to the potential impacts of standardised tobacco packaging as proposed by the guidelines for the international Framework Convention on Tobacco Control: reduced appeal, increased salience and effectiveness of health warnings, and more accurate perceptions of product strength and harm.Methods
Electronic databases were searched and researchers in the field were contacted to identify studies. Eligible studies were published or unpublished primary research of any design, issued since 1980 and concerning tobacco packaging. Twenty-five quantitative studies reported relevant outcomes and met the inclusion criteria. A narrative synthesis was conducted.Results
Studies that explored the impact of package design on appeal consistently found that standardised packaging reduced the appeal of cigarettes and smoking, and was associated with perceived lower quality, poorer taste and less desirable smoker identities. Although findings were mixed, standardised packs tended to increase the salience and effectiveness of health warnings in terms of recall, attention, believability and seriousness, with effects being mediated by the warning size, type and position on pack. Pack colour was found to influence perceptions of product harm and strength, with darker coloured standardised packs generally perceived as containing stronger tasting and more harmful cigarettes than fully branded packs; lighter coloured standardised packs suggested weaker and less harmful cigarettes. Findings were largely consistent, irrespective of location and sample.Conclusions
The evidence strongly suggests that standardised packaging will reduce the appeal of packaging and of smoking in general; that it will go some way to reduce consumer misperceptions regarding product harm based upon package design; and will help make the legally required on-pack health warnings more salient. 相似文献84.
Carmen Capel Irene Albaladejo Isabel Egea Isabel L. Massaretto Fernando J. Yuste-Lisbona Benito Pineda Begoña García-Sogo Trinidad Angosto Francisco B. Flores Vicente Moreno Rafael Lozano María C. Bolarín Juan Capel 《Plant, cell & environment》2020,43(7):1722-1739
Increasing evidences highlight the importance of DEAD-box RNA helicases in plant development and stress responses. In a previous study, we characterized the tomato res mutant (restored cell structure by salinity), showing chlorosis and development alterations that reverted under salt-stress conditions. Map-based cloning demonstrates that RES gene encodes SlDEAD39, a chloroplast-targeted DEAD-box RNA helicase. Constitutive expression of SlDEAD39 complements the res mutation, while the silencing lines had a similar phenotype than res mutant, which is also reverted under salinity. Functional analysis of res mutant proved SlDEAD39 is involved in the in vivo processing of the chloroplast, 23S rRNA, at the hidden break-B site, a feature also supported by in vitro binding experiments of the protein. In addition, our results show that other genes coding for chloroplast-targeted DEAD-box proteins are induced by salt-stress, which might explain the rescue of the res mutant phenotype. Interestingly, salinity restored the phenotype of res adult plants by increasing their sugar content and fruit yield. Together, these results propose an unprecedented role of a DEAD-box RNA helicase in regulating plant development and stress response through the proper ribosome and chloroplast functioning, which, in turn, represents a potential target to improve salt tolerance in tomato crops. 相似文献
85.
Vivas Daniel Grau-Vorster Marta Oliver-Vila Irene García-López Joan Vives Joaquim 《Molecular biology reports》2020,47(7):5145-5154
Molecular Biology Reports - Proper bony tissue regeneration requires mechanical stabilization, an osteogenic biological activity and appropriate scaffolds. The latter two elements can be combined... 相似文献
86.
Bort Alicia Sánchez Belén G. de Miguel Irene Mateos-Gómez Pedro A. Diaz-Laviada Inés 《Molecular biology reports》2020,47(4):2635-2647
Molecular Biology Reports - According to the stem cell theory for cancer, hepatocellular carcinomas are sustained by a group of cancer stem cells (CSCs) which are responsible for resistance to... 相似文献
87.
88.
89.
David P. Mathiasen Irene Gallina Susanne M. Germann Wissam Hamou Morgane Eléouët Sara Thodberg Nadine Eckert-Boulet John Game Michael Lisby 《Gene》2013
Here we report the physical mapping of the rad56-1 mutation to the NAT3 gene, which encodes the catalytic subunit of the NatB N-terminal acetyltransferase in Saccharomyces cerevisiae. Mutation of RAD56 causes sensitivity to X-rays, methyl methanesulfonate, zeocin, camptothecin and hydroxyurea, but not to UV light, suggesting that N-terminal acetylation of specific DNA repair proteins is important for efficient DNA repair. 相似文献
90.
Irene Pérez López Luca Cariolato Darko Maric Ludovic Gillet Hugues Abriel Dario Diviani 《Molecular and cellular biology》2013,33(15):2903-2917
In response to stress, the heart undergoes a remodeling process associated with cardiac hypertrophy that eventually leads to heart failure. A-kinase anchoring proteins (AKAPs) have been shown to coordinate numerous prohypertrophic signaling pathways in cultured cardiomyocytes. However, it remains to be established whether AKAP-based signaling complexes control cardiac hypertrophy and remodeling in vivo. In the current study, we show that AKAP-Lbc assembles a signaling complex composed of the kinases PKN, MLTK, MKK3, and p38α that mediates the activation of p38 in cardiomyocytes in response to stress signals. To address the role of this complex in cardiac remodeling, we generated transgenic mice displaying cardiomyocyte-specific overexpression of a molecular inhibitor of the interaction between AKAP-Lbc and the p38-activating module. Our results indicate that disruption of the AKAP-Lbc/p38 signaling complex inhibits compensatory cardiomyocyte hypertrophy in response to aortic banding-induced pressure overload and promotes early cardiac dysfunction associated with increased myocardial apoptosis, stress gene activation, and ventricular dilation. Attenuation of hypertrophy results from a reduced protein synthesis capacity, as indicated by decreased phosphorylation of 4E-binding protein 1 and ribosomal protein S6. These results indicate that AKAP-Lbc enhances p38-mediated hypertrophic signaling in the heart in response to abrupt increases in the afterload. 相似文献