全文获取类型
收费全文 | 940篇 |
免费 | 113篇 |
出版年
2022年 | 6篇 |
2021年 | 16篇 |
2020年 | 15篇 |
2019年 | 15篇 |
2018年 | 15篇 |
2017年 | 11篇 |
2016年 | 26篇 |
2015年 | 42篇 |
2014年 | 31篇 |
2013年 | 62篇 |
2012年 | 52篇 |
2011年 | 50篇 |
2010年 | 41篇 |
2009年 | 32篇 |
2008年 | 41篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 33篇 |
2004年 | 39篇 |
2003年 | 47篇 |
2002年 | 51篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 19篇 |
1997年 | 14篇 |
1996年 | 7篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1982年 | 11篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1979年 | 8篇 |
1978年 | 12篇 |
1977年 | 7篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1971年 | 8篇 |
1969年 | 5篇 |
1968年 | 5篇 |
1966年 | 5篇 |
1963年 | 5篇 |
1961年 | 6篇 |
1960年 | 5篇 |
排序方式: 共有1053条查询结果,搜索用时 15 毫秒
121.
D Paredes-Sabja G Cofre-Araneda C Brito-Silva M Pizarro-Guajardo MR Sarker 《PloS one》2012,7(8):e43635
Background
Clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. During the course of Clostridium difficile infections (CDI), C. difficile undergoes sporulation and releases spores to the colonic environment. The elevated relapse rates of CDI suggest that C. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment.Methodology/Principal Findings
In this work, we provide evidence that C. difficile spores are well suited to survive the host’s innate immune system. Electron microscopy results show that C. difficile spores are recognized by discrete patchy regions on the surface of macrophage Raw 264.7 cells, and phagocytosis was actin polymerization dependent. Fluorescence microscopy results show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered, and that ∼60% of C. difficile spores were phagocytosed by Raw 264.7 cells. Strikingly, presence of complement decreased Raw 264.7 cells’ ability to phagocytose C. difficile spores. Due to the ability of C. difficile spores to remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of macrophage infection. Interestingly, transmission electron micrographs showed interactions between the surface proteins of C. difficile spores and the phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells with C. difficile spores for 48 h produced significant Raw 264.7 cell death as demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1.Conclusions/Significance
These results demonstrate that despite efficient recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7 cells. 相似文献122.
123.
ABSTRACT: BACKGROUND: Clinical practice guidelines are developed to improve the quality of healthcare. However, clinical guidelines may contribute to health inequities experienced by disadvantaged groups. This study uses an equity lens developed by the International Clinical Epidemiology Network (INCLEN) to examine how well clinical guidelines address inequities experienced by individuals with intellectual disabilities. METHODS: Nine health problems relevant to the health inequities experienced by persons with intellectual disabilities were selected. Clinical guidelines on these disorders were identified from across the world. The INCLEN equity lens was used as the basis for a purposedesigned, semistructured data collection tool. Two raters independently examined each guideline and completed the data collection tool. The data extracted by each rater were discussed at a research group consensus conference and agreement was reached on a final equity lens rating for each guideline. RESULTS: Thirty-six guidelines were identified, one of which (2.8%) explicitly excluded persons with intellectual disabilities. Of the remaining 35, six (17.1%) met the first criterion of the equity lens, identifying persons with intellectual disabilities at high risk for the specific health problem. Eight guidelines (22.9%) contained any content on intellectual disabilities. Six guidelines addressed the fourth equity lens criterion, by giving specific consideration to the barriers to implementation of the guideline in disadvantaged populations. There were no guidelines that addressed the second, third, and fifth equity lens criteria. CONCLUSIONS: The equity lens is a useful tool to systematically examine whether clinical guidelines address the health needs and inequities experienced by disadvantaged groups. Clinical guidelines are likely to further widen the health inequities experienced by persons with intellectual disabilities, and other disadvantaged groups, by being preferentially advantageous to the general population. There is a need to systematically incorporate methods to consider disadvantaged population groups into the processes used to develop clinical guidelines. 相似文献
124.
Keng-Thye Woo Choong-Meng Chan Hui-Lin Choong Han-Kim Tan Marjorie Foo Evan J. C. Lee Chorh-Chuan Tan Grace S. L. Lee Seng-Hoe Tan A. Vathsala Cheng-Hong Lim Gilbert S. C. Chiang Stephanie Fook-Chong Zhao Yi H. B. Tan Kok-Seng Wong 《The HUGO journal》2008,2(3-4):83-91
Background/aims Several studies have reported varying results of the influence of ACE gene on ACEI/ARB therapy. The efficacy of high dose ARB and its influence on ACE gene have not been explored. This is a 6 year randomised trial in IgA nephritis comparing high dose ARB (Losartan 200 mg/day) with normal dose ARB (Losartan 100 mg/day), normal dose ACEI (20 mg/day) and low dose ACEI (10 mg/day). Results Patients on high dose ARB had significantly lower proteinuria, 1.0 ± 0.8 gm/day compared to 1.7 ± 1.0 g/day in the other groups (P = 0.0005). The loss in eGFR was 0.7 ml min?1year?1 for high dose ARB compared to 3.2–3.5 ml min?1year?1 for the other three groups (P = 0.0005). There were more patients on high dose ARB with improvement in eGFR compared to other three groups (P < 0.001). Comparing patients with the three ACE genotypes DD, ID and II, all three groups responded well to therapy with decrease in proteinuria (P < 0.002). Only those on low dose ACEI (10 mg/day) with the I allele had increased in ESRF (P = 0.037). Conclusion High dose ARB is more efficacious in reducing proteinuria and preserving renal function when compared with normal dose ARB and ACEI, and also obviates the genomic influence of ACE gene polymorphism on renal survival. 相似文献
125.
Bcor (BCL6 corepressor) is a widely expressed gene that is mutated in patients with X-linked Oculofaciocardiodental (OFCD) syndrome. BCOR regulates gene expression in association with a complex of proteins capable of epigenetic modification of chromatin. These include Polycomb group (PcG) proteins, Skp-Cullin-F-box (SCF) ubiquitin ligase components and a Jumonji C (Jmjc) domain containing histone demethylase. To model OFCD in mice and dissect the role of Bcor in development we have characterized two loss of function Bcor alleles. We find that Bcor loss of function results in a strong parent-of-origin effect, most likely indicating a requirement for Bcor in extraembryonic development. Using Bcor loss of function embryonic stem (ES) cells and in vitro differentiation assays, we demonstrate that Bcor plays a role in the regulation of gene expression very early in the differentiation of ES cells into ectoderm, mesoderm and downstream hematopoietic lineages. Normal expression of affected genes (Oct3/4, Nanog, Fgf5, Bmp4, Brachyury and Flk1) is restored upon re-expression of Bcor. Consistent with these ES cell results, chimeric animals generated with the same loss of function Bcor alleles show a low contribution to B and T cells and erythrocytes and have kinked and shortened tails, consistent with reduced Brachyury expression. Together these results suggest that Bcor plays a role in differentiation of multiple tissue lineages during early embryonic development. 相似文献
126.
Identification of cold-shock protein RBM3 as a possible regulator of skeletal muscle size through expression profiling 总被引:1,自引:0,他引:1
Dupont-Versteegden EE Nagarajan R Beggs ML Bearden ED Simpson PM Peterson CA 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(4):R1263-R1273
Changes in gene expression associated with skeletal muscle atrophy due to aging are distinct from those due to disuse, suggesting that the response of old muscle to inactivity may be altered. The goal of this study was to identify changes in muscle gene expression that may contribute to loss of adaptability of old muscle. Muscle atrophy was induced in young adult (6-mo) and old (32-mo) male Brown Norway/F344 rats by 2 wk of hindlimb suspension (HS), and soleus muscles were analyzed by cDNA microarrays. Overall, similar changes in gene expression with HS were observed in young and old muscles for genes encoding proteins involved in protein folding (heat shock proteins), muscle structure, and contraction, extracellular matrix, and nucleic acid binding. More genes encoding transport and receptor proteins were differentially expressed in the soleus muscle from young rats, while in soleus muscle from old rats more genes that encoded ribosomal proteins were upregulated. The gene encoding the cold-shock protein RNA-binding motif protein-3 (RBM3) was induced most highly with HS in muscle from old rats, verified by real-time RT-PCR, while no difference with age was observed. The cold-inducible RNA-binding protein (Cirp) gene was also overexpressed with HS, whereas cold-shock protein Y-box-binding protein-1 was not. A time course analysis of RBM3 mRNA abundance during HS showed that upregulation occurred after apoptotic nuclei and markers of protein degradation increased. We conclude that a cold-shock response may be part of a compensatory mechanism in muscles undergoing atrophy to preserve remaining muscle mass and that RBM3 may be a therapeutic target to prevent muscle loss. 相似文献
127.
128.
Comparison of the Menopause and Midlife Transition between Japanese American and European American Women 总被引:1,自引:0,他引:1
Marjorie Kagawa-Singer Katherine Wu Yuko Kawanishi Gail A. Greendale Sue Kim Shelley R. Adler Nancy Wongvipat 《Medical anthropology quarterly》2002,16(1):64-91
Cross-cultural differences in the meaning and experience of the universal biologic phenomenon of the menopause have been well documented. Very few studies, however, have focused on the response to the midlife transition among ethnic minority women in the United States, and even fewer exist about Asian American women. This exploratory study compared the perceptions and experiences of the midlife transition among Japanese American and European American women. The midlife transition was viewed as a time of self-assurance, maturity, and taking comfort and satisfaction in oneself. Biologically, it was a marker of mortality. Similar to menses, marriage, and motherhood, menopause was viewed as the final identity transformation, but interpreted quite differently by the two ethnic groups. The findings of this study support the cross-cultural theories that emphasize the interaction of biology, society, age, gender, and acculturation in this universal female experience and suggest additional expansion of these theories to incorporate lifestyle choices that may affect the actual health consequences of female aging. [menopause, midlife transition, Japanese American women, ethnicity] 相似文献
129.
Factors Associated with Slow Disease Progression in Macaques Immunized with an Adenovirus-Simian Immunodeficiency Virus (SIV) Envelope Priming-gp120 Boosting Regimen and Challenged Vaginally with SIVmac251
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
130.
Studies of highly kin-structured mammal societies have revealedthe importance of natal philopatry in determining the distributionof genetic variation within populations. In comparison, therelationship between philopatry and genetic diversity withinpopulations of moderately kin-structured societies has receivedrelatively little attention. Previous studies of Neotoma macrotishave suggested that females form distinct kin clusters. Eachkin cluster overlaps spatially with the home range(s) of oneor more males that are not related to each other or to the femaleswith which they are spatially associated. To examine interactionsbetween philopatry and genetic structure in this apparentlymoderately kin-structured species, we characterized spatialand genetic relationships among individually marked femalesin a population of N. macrotis from central coastal California.Our field studies revealed that, contrary to expectation, femalesin this population were not strongly philopatric and spatiallyclustered females were not characterized by high levels of geneticrelatedness. Nevertheless, genetic structure was evident withinthe study population; spatial and genetic distances among femaleswere significantly correlated, suggesting that dispersal patternsinfluenced genetic structure even in the absence of marked femalephilopatry. Because females with overlapping spatial distributionswere not typically closely related to one another, opportunitiesfor the evolution of kin-selected social behavior (e.g., cooperativecare of young) appear to be limited in this population. 相似文献