全文获取类型
收费全文 | 167篇 |
免费 | 11篇 |
国内免费 | 6篇 |
专业分类
184篇 |
出版年
2024年 | 1篇 |
2022年 | 4篇 |
2021年 | 3篇 |
2020年 | 4篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 8篇 |
2014年 | 8篇 |
2013年 | 10篇 |
2012年 | 26篇 |
2011年 | 12篇 |
2010年 | 11篇 |
2009年 | 8篇 |
2008年 | 5篇 |
2007年 | 6篇 |
2006年 | 7篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1943年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有184条查询结果,搜索用时 0 毫秒
161.
Tedros A Ghebreyesus Mitiku Haile Karen H Witten Asefaw Getachew Ambachew M Yohannes Mekonnen Yohannes Hailay D Teklehaimanot Steven W Lindsay Peter Byass 《BMJ (Clinical research ed.)》1999,319(7211):663-666
ObjectiveTo assess the impact of construction of microdams on the incidence of malaria in nearby communities in terms of possibly increasing peak incidence and prolonging transmission.DesignFour quarterly cycles of malaria incidence surveys, each taking 30 days, undertaken in eight at risk communities close to dams paired with eight control villages at similar altitudes but beyond flight range of mosquitoes.SettingTigray region in northern Ethiopia at altitudes of 1800 to 2225 m.SubjectsAbout 7000 children under 10 years living in villages within 3 km of microdams and in control villages 8-10 km distant.ResultsOverall incidence of malaria for the villages close to dams was 14.0 episodes/1000 child months at risk compared with 1.9 in the control villages—a sevenfold ratio. Incidence was significantly higher in both communities at altitudes below 1900 m.ConclusionsThere is a need for attention to be given to health issues in the implementation of ecological and environmental development programmes, specifically for appropriate malaria control measures to counteract the increased risks near these dams.
Key messages
- Environmental development may have important effects on the epidemiology of vector borne diseases such as malaria
- This may be particularly important where disease transmission is unstable—for example, in highland areas
- Children in villages near recently constructed microdams in northern Ethiopia had a significantly increased risk of malaria
- It seems that this irrigation development programme is leading to increased malaria transmission across a range of altitudes and seasons
- Intersectoral collaboration is necessary in development projects that may affect communities both positively and negatively
162.
Allelic variation at the 3'-end of the vitamin D receptor (VDR) gene has been associated with a 3-5-fold increased risk of developing prostate cancer and with differences in bone mineralization. This genetic diversity does not alter the VDR protein structurally, but instead may be a marker(s) of other, nearby polymorphisms that influence message stability or translation. The work reported here was instigated to identify additional VDR 3'-UTR polymorphisms that may have functional significance and to then test whether these genetic variants alter message stability. Initially, four novel, frequently occurring sequence variants were identified that associated with two common haplotypes that were described previously. These common sequence variants were not found within three message-destabilizing elements that we mapped within the 3'-UTR of the vitamin D receptor mRNA. Furthermore, the two VDR 3'-UTR haplotypes conferred an identical half-life on a heterologous beta-globin reporter gene, in an in vitro assay. We therefore conclude that common polymorphisms within the VDR 3'-UTR do not influence message stability. 相似文献
163.
Yang F Liu XB Quinones M Melby PC Ghio A Haile DJ 《The Journal of biological chemistry》2002,277(42):39786-39791
Acute and chronic inflammation cause many changes in total body iron metabolism including the sequestration of iron in phagocytic cells of the reticuloendothelial system. This change in iron metabolism contributes to the development of the anemia of inflammation. MTP1, the duodenal enterocyte basolateral iron exporter, is also expressed in the cells of the reticuloendothelial system (RES) and is likely to be involved in iron recycling of these cells. In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation. The down-regulation of splenic expression of MTP1 by inflammation was also observed in a Leishmania donovani model of chronic infection. The response of MTP1 to lipopolysaccharide (LPS) requires signaling through the LPS receptor, Toll-like receptor 4 (TLR4). In mice lacking TLR4, MTP1 expression is not altered in response to LPS. In addition, mice lacking tumor necrosis factor-receptor 1a respond appropriately to LPS with down-regulation of MTP1, despite hyporesponsiveness to tumor necrosis factor-alpha signaling, suggesting that this cytokine may not be required for the LPS effect. We hypothesize that the iron sequestration in the RES system that accompanies inflammation is because of down-regulation of MTP1. 相似文献
164.
During MJ Cao L Zuzga DS Francis JS Fitzsimons HL Jiao X Bland RJ Klugmann M Banks WA Drucker DJ Haile CN 《Nature medicine》2003,9(9):1173-1179
Glucagon-like peptide-1 (GLP-1) is a gut peptide that, together with its receptor, GLP-1R, is expressed in the brain. Here we show that intracerebroventricular (i.c.v.) GLP-1 and [Ser(2)]exendin(1-9) (HSEGTFTSD; homologous to a conserved domain in the glucagon/GLP-1 family) enhance associative and spatial learning through GLP-1R. [Ser(2)]exendin(1-9), but not GLP-1, is also active when administered peripherally. GLP-1R-deficient mice have a phenotype characterized by a learning deficit that is restored after hippocampal Glp1r gene transfer. In addition, rats overexpressing GLP-1R in the hippocampus show improved learning and memory. GLP-1R-deficient mice also have enhanced seizure severity and neuronal injury after kainate administration, with an intermediate phenotype in heterozygotes and phenotypic correction after Glp1r gene transfer in hippocampal somatic cells. Systemic administration of [Ser(2)]exendin(1-9) in wild-type animals prevents kainate-induced apoptosis of hippocampal neurons. Brain GLP-1R represents a promising new target for both cognitive-enhancing and neuroprotective agents. 相似文献
165.
An arsenate reductase from Synechocystis sp. strain PCC 6803 exhibits a novel combination of catalytic characteristics 下载免费PDF全文
The deduced protein product of open reading frame slr0946 from Synechocystis sp. strain PCC 6803, SynArsC, contains the conserved sequence features of the enzyme superfamily that includes the low-molecular-weight protein-tyrosine phosphatases and the Staphylococcus aureus pI258 ArsC arsenate reductase. The recombinant protein product of slr0946, rSynArsC, exhibited vigorous arsenate reductase activity (V(max) = 3.1 micro mol/min. mg), as well as weak phosphatase activity toward p-nitrophenyl phosphate (V(max) = 0.08 micro mol/min. mg) indicative of its phosphohydrolytic ancestry. pI258 ArsC from S. aureus is the prototype of one of three distinct families of detoxifying arsenate reductases. The prototypes of the others are Acr2p from Saccharomyces cerevisiae and R773 ArsC from Escherichia coli. All three have converged upon catalytic mechanisms involving an arsenocysteine intermediate. While SynArsC is homologous to pI258 ArsC, its catalytic mechanism exhibited a unique combination of features. rSynArsC employed glutathione and glutaredoxin as the source of reducing equivalents, like Acr2p and R773 ArsC, rather than thioredoxin, as does the S. aureus enzyme. As postulated for Acr2p and R773 ArsC, rSynArsC formed a covalent complex with glutathione in an arsenate-dependent manner. rSynArsC contains three essential cysteine residues like pI258 ArsC, whereas the yeast and E. coli enzymes require only one cysteine for catalysis. As in the S. aureus enzyme, these "extra" cysteines apparently shuttle a disulfide bond to the enzyme's surface to render it accessible for reduction. SynArsC and pI258 ArsC thus appear to represent alternative branches in the evolution of their shared phosphohydrolytic ancestor into an agent of arsenic detoxification. 相似文献
166.
167.
Predictor of multidrug resistant tuberculosis in southwestern part of Ethiopia: a case control study
Dabesa Gobena Gemechu Ameya Kinfe Haile Getaneh Abreha Yoseph Worku Tessema Debela 《Annals of clinical microbiology and antimicrobials》2018,17(1):30
Background
Curable disease tuberculosis is becoming incurable or difficult to treat due to drug resistance. Multi drug resistance tuberculosis is a major health problem for less developed countries. Development of drug resistance is mainly as result of man related factors and poor lifestyle. Identifying predictors of drug resistance and working on them is the important way of reducing the expansion in high burden countries. Ethiopia is one of TB, TB/HIV, and multi-drug resistant tuberculosis (MDR-TB) high burden country globally. This study was aimed to assess predictor of MDR-TB in southwest part of Ethiopia.Methods
Unmatched case control study was conducted in case to control ratio of 1:1.2 in southwest part of Ethiopia. The cases were recruited from confirmed MDR-TB patient enrolled on second line treatment in Shenen Gibe Hospital (MDR-TB treatment center of the prefecture) and the controls were recruited from previously TB patients who cured or patient with smear negative at the end of treatment month during the study period in the same area. The data was collected by structured questionnaire by interview and logistic regression analyses were used to identify predictors of MDR-TB. Odds ratios with 95% CI were computed to determine the predictors.Result
From the total 132 participants about 45% of them were cases. None disclosed tuberculosis infected to relatives [AOR?=?3.4, 95% CI (1.2–9.8)], insufficient instruction on how to take anti-TB drug [AOR?=?4.7, 95% CI (1.4–14.6)], contact history with MDR-TB [AOR?=?8.5, 95% CI (2.9–25.5)], interruption of first-line anti-TB treatment for at list 1 day [AOR?=?7.9, 95% CI (2.5–24.9)], and having alcohol drinking habits [AOR?=?5.1, 95% CI (1.4–18.7)] were identified predictors for MDR-TB infection in study area.Conclusion
TB infection disclosure status, insufficient instruction on drug usage, contact history with MDR-TB, interruption of first-line anti-TB drugs, and alcohol drinking habits were identified predictor of MDR-TB case. Therefore, early detection and proper treatment of drug susceptible TB, strengthening directly observed treatment, short-course on daily bases, community involvement, and supporting the patient to intervene identified factors is paramount.168.
169.
David J. Rickard Clark A. Sehon Viera Kasparcova Lorena A. Kallal Xin Zeng Monica N. Montoute Tushar Chordia Derek D. Poore Hu Li Zining Wu Patrick M. Eidam Pamela A. Haile Jong Yu John G. Emery Robert W. Marquis Peter J. Gough John Bertin 《PloS one》2013,8(8)
NOD2 is an intracellular pattern recognition receptor that assembles with receptor-interacting protein (RIP)-2 kinase in response to the presence of bacterial muramyl dipeptide (MDP) in the host cell cytoplasm, thereby inducing signals leading to the production of pro-inflammatory cytokines. The dysregulation of NOD2 signaling has been associated with various inflammatory disorders suggesting that small-molecule inhibitors of this signaling complex may have therapeutic utility. To identify inhibitors of the NOD2 signaling pathway, we utilized a cell-based screening approach and identified a benzimidazole diamide compound designated GSK669 that selectively inhibited an MDP-stimulated, NOD2-mediated IL-8 response without directly inhibiting RIP2 kinase activity. Moreover, GSK669 failed to inhibit cytokine production in response to the activation of Toll-like receptor (TLR)-2, tumor necrosis factor receptor (TNFR)-1 and closely related NOD1, all of which share common downstream components with the NOD2 signaling pathway. While the inhibitors blocked MDP-induced NOD2 responses, they failed to block signaling induced by NOD2 over-expression or single stranded RNA, suggesting specificity for the MDP-induced signaling complex and activator-dependent differences in NOD2 signaling. Investigation of structure-activity relationship allowed the identification of more potent analogs that maintained NOD2 selectivity. The largest boost in activity was achieved by N-methylation of the C2-ethyl amide group. These findings demonstrate that the NOD2 signaling pathway is amenable to modulation by small molecules that do not target RIP2 kinase activity. The compounds we identified should prove useful tools to investigate the importance of NOD2 in various inflammatory processes and may have potential clinical utility. 相似文献
170.
Isabel Martinez-Pino Francisco J. Luquero Ké?ta Sakoba Souleymane Sylla Melatwork Haile Rebecca F. Grais Iza Ciglenecki Marie-Laure Quilici Anne-Laure Page 《PLoS neglected tropical diseases》2013,7(8)