全文获取类型
收费全文 | 540篇 |
免费 | 45篇 |
专业分类
585篇 |
出版年
2023年 | 4篇 |
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 5篇 |
2016年 | 14篇 |
2015年 | 21篇 |
2014年 | 13篇 |
2013年 | 30篇 |
2012年 | 41篇 |
2011年 | 25篇 |
2010年 | 13篇 |
2009年 | 16篇 |
2008年 | 24篇 |
2007年 | 26篇 |
2006年 | 27篇 |
2005年 | 21篇 |
2004年 | 21篇 |
2003年 | 18篇 |
2002年 | 24篇 |
2001年 | 19篇 |
2000年 | 21篇 |
1999年 | 14篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 15篇 |
1991年 | 10篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 5篇 |
1987年 | 10篇 |
1985年 | 3篇 |
1983年 | 8篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有585条查询结果,搜索用时 15 毫秒
71.
Brian M.O. Ogendi Rakesh K. Bakshi Kanupriya Gupta Richa Kapil LaDraka T. Brown Stephen J. Jordan Steffanie Sabbaj Christen G. Press Jeannette Y. Lee William M. Geisler 《Microbes and infection / Institut Pasteur》2018,20(3):176-184
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4+ and CD8+ T cells expressing these markers. These findings suggest a dynamic interplay of CD4+ and CD8+ T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection, a significantly higher proportion of CD8+ T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections. 相似文献
72.
Aniek Boers Lorian Slagter-Menkema Bettien M. van Hemel Jerome L. Belinson Teus Ruitenbeek Henk J. Buikema Harry Klip Hilde Ghyssaert Ate G. J. van der Zee Geertruida H. de Bock G. Bea A. Wisman Ed Schuuring 《PloS one》2014,9(7)
The diagnostic performance of the widely-used Cervista HPV HR test was compared to the Hybrid Capture 2 (HC2) test in a Dutch population-based cervical cancer screening program. In 900 scrapings of women with normal cytomorphology, specificity was 90% (95%CI: 87.84–91.87) for the Cervista HPV HR test and 96% (95%CI: 94.76–97.37) for the HC2 test with 93% agreement between both tests (κ = 0.5, p<0.001). The sensitivity for CIN2+ using 65 scrapings of women with histological-confirmed CIN2+ was 91% (95%CI: 80.97–96.51) for the Cervista HPV HR test and 92% (95%CI: 82.94–97.43) for the HC2 test with 95% agreement between both tests (κ = 0.7, p<0.001). Fifty-seven of 60 HC2 negative/Cervista positive cases tested HPV-negative with PCR-based HPV assays; of these cases 56% were defined as Cervista triple-positive with FOZ values in all 3 mixes higher than the second cut-off of 1.93 (as set by manufacturer). By setting this cut-off at 5.0, specificity improved significantly without affecting sensitivity. External validation of this new cut-off at 5.0 in triple-positive scrapings of women selected from the SHENCCASTII database revealed that 22/24 histological normal cases now tested HPV-negative in the Cervista HPV HR test, while CIN2+ lesions remained HPV-positive. The intra-laboratory reproducibility of the Cervista HPV HR test (n = 510) showed a concordance of 92% and 93% for cut-off 1.93 and 5.0 (κ = 0.83 and κ = 0.84, p<0.001) and inter-laboratory agreement of the Cervista HPV HR test was 90% and 93% for cut-off 1.93 and 5.0 (κ = 0.80 and κ = 0.85, p<0.001). In conclusion, the specificity of the Cervista HPV HR test could be improved significantly by increasing the second cut-off from 1.93 to 5.0, without affecting the sensitivity of the test in a population-based screening setting. 相似文献
73.
Peukert S Sun Y Zhang R Hurley B Sabio M Shen X Gray C Dzink-Fox J Tao J Cebula R Wattanasin S 《Bioorganic & medicinal chemistry letters》2008,18(6):1840-1844
Based on a pharmacophore hypothesis substituted tetramic and tetronic acid 3-carboxamides as well as dihydropyridin-2-one-3-carboxamides were investigated as inhibitors of undecaprenyl pyrophosphate synthase (UPPS) for use as novel antimicrobial agents. Synthesis and structure-activity relationship patterns for this class of compounds are discussed. Selectivity data and antibacterial activities for selected compounds are provided. 相似文献
74.
75.
Antibodies have been raised against an enriched preparation of isolated rat cerebellar Purkinje cells. The immunoglobulins were labeled with 125I and the strength and specificity of the serum determined by a direct binding assay on cerebellar membranes. About 2% of the 125I-labeled IgG bound to an excess of cerebellar membranes. Absorption with heart and liver membranes removed 80.5% of the 125I-labeled IgG binding to cerebellar membranes; absorption with cerebrum membranes removed 13% more; the remaining 6.5% were directed specifically against cerebellar membranes. An enriched 125I-labeled anti-Purkinje antibody population was prepared by absorption and subsequent elution from cerebellar membranes. The absorption pattern with heart, liver, and cerebrum membranes resembled that found with the total population of IgG except that the nonspecific binding was significantly diminished. The Purkinje cell degeneration (pcd) mouse mutant was used to assess the specificity of the serum toward the Purkinje cells. After absorption of the enriched anti-Purkinje antibodies with heart, liver, and cerebrum membranes, the binding of labeled IgG to membranes prepared from pcd/pcd cerebella was about one-fourth that found with control cerebella. The direct immunoperoxidase technique performed on smears of purified Purkinje and granule cells shows that the unabsorbed serum stains both classes of cells, but that after absorption with liver, heart, and cerebrum membranes, only the Purkinje cells react positively. 相似文献
76.
The habitat and conduit functions of roads in the spread of three invasive plant species 总被引:2,自引:0,他引:2
Nonnative plant species commonly occur along roadsides, and populations are often assumed to invade by spread along the road
axis. To distinguish between the function of roadsides as movement corridors and as habitat, nonnative plant species were
surveyed along roads in deciduous forest sites in southeastern Ohio, USA. The importance of road proximity was tested by comparing
nonnative species abundance in 100 m transects along roads with transects in undisturbed forest. Nonnative species were most
abundant and most frequently observed in roadside sites in valleys. Three common species were chosen for closer scrutiny.
In a seed sowing experiment roads and open sites proved to be better locations for the germination and growth of Microstegium vimineum than non-roadside and closed-canopy sites. Tussilago farfara and Rosa multiflora occurred in a small number of disjunct patches suggesting infrequent arrival in the sampled transects. Both species were
strongly clustered at scales consistent with diffusive spread by vegetative growth and short-range seed dispersal. Comparisons
of distributions parallel and perpendicular to roads showed no evidence for enhanced dispersal along the road axis. Microstegium distributions were correlated with local light availability implying site saturation. Microstegium micro-distributions suggested that spread along the road axis was facilitated by movement of dormant seeds in road maintenance.
Thus, roadsides appear to function as both habitat and a conduit for population expansion, with the rate of spread dependent
on the life history of the individual species. These results suggest a hierarchical process of regional invasion, with different
dispersal mechanisms functioning at different spatial scales. 相似文献
77.
Tim G. A. M. Wolfs Wim A. Buurman Bea Zoer Rob M. J. Moonen Joep P. M. Derikx Geertje Thuijls Eduardo Villamor Markus Gantert Yves Garnier Luc J. I. Zimmermann Boris W. Kramer 《PloS one》2009,4(6)
Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis.Chorioamnionitis was induced at different gestational ages (GA). Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d) inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO) donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase.Our results indicate that the distribution of the tight junctional protein ZO-1, the immune defence and vascular function are immature at low GA and are further compromised by endotoxin-induced chorioamnionitis. This study suggests that both prematurity and inflammation in utero disturb fetal gut development, potentially predisposing to postnatal intestinal pathology. 相似文献
78.
Daniel M?usezahl Andri Christen Gonzalo Duran Pacheco Fidel Alvarez Tellez Mercedes Iriarte Maria E. Zapata Myriam Cevallos Jan Hattendorf Monica Daigl Cattaneo Benjamin Arnold Thomas A. Smith John M. Colford Jr 《PLoS medicine》2009,6(8)
Background
Solar drinking water disinfection (SODIS) is a low-cost, point-of-use water purification method that has been disseminated globally. Laboratory studies suggest that SODIS is highly efficacious in inactivating waterborne pathogens. Previous field studies provided limited evidence for its effectiveness in reducing diarrhoea.Methods and Findings
We conducted a cluster-randomized controlled trial in 22 rural communities in Bolivia to evaluate the effect of SODIS in reducing diarrhoea among children under the age of 5 y. A local nongovernmental organisation conducted a standardised interactive SODIS-promotion campaign in 11 communities targeting households, communities, and primary schools. Mothers completed a daily child health diary for 1 y. Within the intervention arm 225 households (376 children) were trained to expose water-filled polyethyleneteraphtalate bottles to sunlight. Eleven communities (200 households, 349 children) served as a control. We recorded 166,971 person-days of observation during the trial representing 79.9% and 78.9% of the total possible person-days of child observation in intervention and control arms, respectively. Mean compliance with SODIS was 32.1%. The reported incidence rate of gastrointestinal illness in children in the intervention arm was 3.6 compared to 4.3 episodes/year at risk in the control arm. The relative rate of diarrhoea adjusted for intracluster correlation was 0.81 (95% confidence interval 0.59–1.12). The median length of diarrhoea was 3 d in both groups.Conclusions
Despite an extensive SODIS promotion campaign we found only moderate compliance with the intervention and no strong evidence for a substantive reduction in diarrhoea among children. These results suggest that there is a need for better evidence of how the well-established laboratory efficacy of this home-based water treatment method translates into field effectiveness under various cultural settings and intervention intensities. Further global promotion of SODIS for general use should be undertaken with care until such evidence is available.Trial Registration
www.ClinicalTrials.gov Please see later in the article for Editors'' Summary NCT00731497相似文献79.
80.
Simona E Budulac Dirkje S Postma Pieter S Hiemstra Lisette IZ Kunz Mateusz Siedlinski Henriette A Smit Judith M Vonk Bea Rutgers Wim Timens H Marike Boezen the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease study group 《Respiratory research》2010,11(1):60