全文获取类型
收费全文 | 174篇 |
免费 | 9篇 |
出版年
2022年 | 1篇 |
2021年 | 6篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 10篇 |
2013年 | 12篇 |
2012年 | 11篇 |
2011年 | 16篇 |
2010年 | 12篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 6篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 1篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 6篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1978年 | 2篇 |
1976年 | 4篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1968年 | 2篇 |
1966年 | 1篇 |
1963年 | 1篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有183条查询结果,搜索用时 31 毫秒
91.
Reina JA de Kinderen Danielle AJE Lambrechts Debby Postulart Alfons GH Kessels Jos GM Hendriksen Albert P Aldenkamp Marian HJM Majoie 《BMC neurology》2011,11(1):10
Background
Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. 相似文献92.
Dolff S Abdulahad WH Westra J Doornbos-van der Meer B Limburg PC Kallenberg CG Bijl M 《Arthritis research & therapy》2011,13(5):R157
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients. 相似文献93.
Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations
Deena A Abdulahad Johanna Westra Johannes Bijzet Sebastian Dolff Marcory C van Dijk Pieter C Limburg Cees GM Kallenberg Marc Bijl 《Arthritis research & therapy》2012,14(4):R184
Introduction
Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE. Urinary excretion of HMGB1 might reflect renal inflammatory injury. To assess whether urinary HMGB1 reflects renal inflammation we determined serum levels of HMGB1 simultaneously with its urinary levels in SLE patients with and without LN in comparison to healthy controls (HC). We also analyzed urinary HMGB1 levels in relation with clinical and serological disease activity.Methods
The study population consisted of 69 SLE patients and 17 HC. Twenty-one patients had biopsy proven active LN, 15 patients had a history of LN without current activity, and 33 patients had non-renal SLE. Serum and urine levels of HMGB1 were both measured by western blotting. Clinical and serological parameters were assessed according to routine procedures. In 17 patients with active LN a parallel analysis was performed on the expression of HMGB1 in renal biopsies.Results
Serum and urinary levels of HMGB1 were significantly increased in patients with active LN compared to patients without active LN and HC. Similarly, renal tissue of active LN patients showed strong expression of HMGB1 at cytoplasmic and extracellular sites suggesting active release of HMGB1. Serum and urinary levels in patients without active LN were also significantly higher compared to HC. Urinary HMGB1 levels correlated with SLEDAI, and showed a negative correlation with complement C3 and C4.Conclusion
Levels of HMGB1 in urine of SLE patients, in particular in those with active LN, are increased and correlate with SLEDAI scores. Renal tissue of LN patients shows increased release of nuclear HMGB1 compared to control renal tissue. HMGB1, although at lower levels, is, however, also present in the urine of patients without active LN. These data suggest that urinary HMGB1 might reflect both local renal inflammation as well as systemic inflammation. 相似文献94.
Suzanne Arends Anneke Spoorenberg Pieternella M Houtman Martha K Leijsma Reinhard Bos Cees GM Kallenberg Henk Groen Elisabeth Brouwer Eveline van der Veer 《Arthritis research & therapy》2012,14(2):R98
Introduction
The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).Methods
This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.Results
After three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician''s global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.Conclusions
Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures. 相似文献95.
Tree species are expected to track warming climate by shifting their ranges to higher latitudes or elevations, but current evidence of latitudinal range shifts for suites of species is largely indirect. In response to global warming, offspring of trees are predicted to have ranges extend beyond adults at leading edges and the opposite relationship at trailing edges. Large‐scale forest inventory data provide an opportunity to compare present latitudes of seedlings and adult trees at their range limits. Using the USDA Forest Service's Forest Inventory and Analysis data, we directly compared seedling and tree 5th and 95th percentile latitudes for 92 species in 30 longitudinal bands for 43 334 plots across the eastern United States. We further compared these latitudes with 20th century temperature and precipitation change and functional traits, including seed size and seed spread rate. Results suggest that 58.7% of the tree species examined show the pattern expected for a population undergoing range contraction, rather than expansion, at both northern and southern boundaries. Fewer species show a pattern consistent with a northward shift (20.7%) and fewer still with a southward shift (16.3%). Only 4.3% are consistent with expansion at both range limits. When compared with the 20th century climate changes that have occurred at the range boundaries themselves, there is no consistent evidence that population spread is greatest in areas where climate has changed most; nor are patterns related to seed size or dispersal characteristics. The fact that the majority of seedling extreme latitudes are less than those for adult trees may emphasize the lack of evidence for climate‐mediated migration, and should increase concerns for the risks posed by climate change. 相似文献
96.
Andrew J. Grant Christopher Coward Michael A. Jones Claire A. Woodall Paul A. Barrow Duncan J. Maskell 《Applied microbiology》2005,71(12):8031-8041
We have constructed plasmids to be used for in vitro signature-tagged mutagenesis (STM) of Campylobacter jejuni and used these to generate STM libraries in three different strains. Statistical analysis of the transposon insertion sites in the C. jejuni NCTC 11168 chromosome and the plasmids of strain 81-176 indicated that their distribution was not uniform. Visual inspection of the distribution suggested that deviation from uniformity was not due to preferential integration of the transposon into a limited number of hot spots but rather that there was a bias towards insertions around the origin. We screened pools of mutants from the STM libraries for their ability to colonize the ceca of 2-week-old chickens harboring a standardized gut flora. We observed high-frequency random loss of colonization proficient mutants. When cohoused birds were individually inoculated with different tagged mutants, random loss of colonization-proficient mutants was similarly observed, as was extensive bird-to-bird transmission of mutants. This indicates that the nature of campylobacter colonization in chickens is complex and dynamic, and we hypothesize that bottlenecks in the colonization process and between-bird transmission account for these observations. 相似文献
97.
Robert E. S. Bain Claire Woodall John Elliott Benjamin F. Arnold Rosalind Tung Robert Morley Martella du Preez Jamie K. Bartram Anthony P. Davis Stephen W. Gundry Stephen Pedley 《PloS one》2015,10(10)
The cost and complexity of traditional methods for the detection of faecal indicator bacteria, including E. coli, hinder widespread monitoring of drinking water quality, especially in low-income countries and outside controlled laboratory settings. In these settings the problem is exacerbated by the lack of inexpensive media for the detection of E. coli in drinking water. We developed a new low-cost growth medium, aquatest (AT), and validated its use for the direct detection of E. coli in temperate and sub-tropical drinking waters using IDEXX Quanti-Tray®. AT was compared with IDEXX Colilert-18® and either EC-MUG or MLSB for detecting low levels of E. coli from water samples from temperate (n = 140; Bristol, UK) and subtropical regions (n = 50, Pretoria/Tshwane, South Africa). Confirmatory testing (n = 418 and 588, respectively) and the comparison of quantitative results were used to assess performance. Sensitivity of AT was higher than Colilert-18® for water samples in the UK [98.0% vs. 86.9%; p<0.0001] and South Africa [99.5% vs. 93.2%; p = 0.0030]. There was no significant difference in specificity, which was high for both media (>95% in both settings). Quantitative results were comparable and within expected limits. AT is reliable and accurate for the detection of E. coli in temperate and subtropical drinking water. The composition of the new medium is reported herein and can be used freely. 相似文献
98.
Lukoye Atwoli Abdullah H. Baqui Thomas Benfield Raffaella Bosurgi Fiona Godlee Stephen Hancocks Richard Horton Laurie Laybourn-Langton Carlos Augusto Monteiro Ian Norman Kirsten Patrick Nigel Praities Marcel GM Olde Rikkert Eric J. Rubin Peush Sahni Richard Smith Nick Talley Sue Turale Damin Vzquez 《PLoS medicine》2021,18(9)
99.
Hettema ME Zhang D de Leeuw K Stienstra Y Smit AJ Kallenberg CG Bootsma H 《Arthritis research & therapy》2008,10(2):R49
Introduction
Several systemic autoimmune diseases are associated with an increased prevalence of atherosclerosis which could not be explained by traditional risk factors alone. In systemic sclerosis (SSc), microvascular abnormalities are well recognized. Previous studies have suggested an increased prevalence of macrovascular disease as well. We compared patients with SSc to healthy controls for signs of early atherosclerosis by measuring intima-media thickness (IMT) of the common carotid artery in relation to traditional risk factors and markers of endothelial activation. 相似文献100.
Anton?C?van de Vusse Suzanne?GM?Stomp-van den Berg Alfons?HF?Kessels Wim?EJ?WeberEmail author 《BMC neurology》2004,4(1):13