全文获取类型
收费全文 | 304篇 |
免费 | 17篇 |
出版年
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 14篇 |
2014年 | 15篇 |
2013年 | 23篇 |
2012年 | 13篇 |
2011年 | 14篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 13篇 |
2007年 | 13篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 11篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 9篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 16篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有321条查询结果,搜索用时 15 毫秒
121.
Maarten van den Berge Wim CJ Hop Thys van der Molen Jan A van Noord Jacques PHM Creemers Ad JM Schreurs Emiel FM Wouters Dirkje S Postma 《Respiratory research》2012,13(1):44
Background
Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.Methods
In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.Results
There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.Conclusions
Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice. 相似文献122.
Tom?PMM?VluggenEmail author Jolanda?CM?van Haastregt Jeanine?A?Verbunt Elly?JM?Keijsers Jos?MGA?Schols 《BMC neurology》2012,12(1):164
Background
Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.Methods
A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.Trial registration
International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR2412123.
Background
The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage. 相似文献124.
Esther Heikens Masja Leendertse Lucas M Wijnands Miranda van Luit-Asbroek Marc JM Bonten Tom van der Poll Rob JL Willems 《BMC microbiology》2009,9(1):19-7
Background
Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice. 相似文献125.
Hetty C van den Broeck Teun WJM van Herpen Cees Schuit Elma MJ Salentijn Liesbeth Dekking Dirk Bosch Rob J Hamer Marinus JM Smulders Ludovicus JWJ Gilissen Ingrid M van der Meer 《BMC plant biology》2009,9(1):41
Background
Gluten proteins can induce celiac disease (CD) in genetically susceptible individuals. In CD patients gluten-derived peptides are presented to the immune system, which leads to a CD4+ T-cell mediated immune response and inflammation of the small intestine. However, not all gluten proteins contain T-cell stimulatory epitopes. Gluten proteins are encoded by multigene loci present on chromosomes 1 and 6 of the three different genomes of hexaploid bread wheat (Triticum aestivum) (AABBDD). 相似文献126.
Wouter N Leonhard Jeroen H Roelfsema Irma S Lantinga-van Leeuwen Martijn H Breuning Dorien JM Peters 《BMC biotechnology》2008,8(1):18
Background
Inducible conditional knockout animals are widely used to get insight in the function of genes and the pathogenesis of human diseases. These models frequently rely on Cre-mediated recombination of sequences flanked by Lox-P sites. To understand the consequences of gene disruption, it is essential to know the efficiency of the recombination process. 相似文献127.
Joost LM Vissers Betty CAM van Esch Prescilla V Jeurink Gerard A Hofman Antoon JM van Oosterhout 《Respiratory research》2004,5(1):21
BackgroundPreviously, we demonstrated that OVA-loaded macrophages (OVA-Mφ) partially suppress OVA-induced airway manifestations of asthma in BALB/c mice. In vitro studies showed that OVA-Mφ start to produce IL-10 upon interaction with allergen-specific T cells, which might mediate their immunosuppressive effects. Herein, we examined whether IL-10 is essential for the immunosuppressive effects of OVA-Mφ in vivo, and whether ex vivo stimulation of the IL-10 production by OVA-Mφ could enhance these effects.MethodsPeritoneal Mφ were loaded with OVA and stimulated with LPS or immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) in vitro. The increase of IL-10 production was examined and, subsequently, ex vivo stimulated OVA-Mφ were used to treat (i.v.) OVA-sensitized mice. To further explore whether Mφ-derived IL-10 mediates the immunosuppressive effects, Mφ isolated from IL-10-/- mice were used for treatment.ResultsWe found that stimulation with LPS or ISS-ODN highly increased the IL-10 production by OVA-Mφ (2.5-fold and 4.5-fold increase, respectively). ISS-ODN stimulation of OVA-Mφ significantly potentiated the suppressive effects on allergic airway inflammation. Compared to sham-treatment, ISS-ODN-stimulated OVA-Mφ suppressed the airway eosinophilia by 85% (vs. 30% by unstimulated OVA-Mφ), IL-5 levels in bronchoalveolar lavage fluid by 80% (vs. 50%) and serum OVA-specific IgE levels by 60% (vs. 30%). Importantly, IL-10-/-Mφ that were loaded with OVA and stimulated with ISS-ODN ex vivo, failed to suppress OVA-induced airway inflammation.ConclusionsThese results demonstrate that Mφ-derived IL-10 mediates anti-inflammatory responses in a mouse model of allergic asthma, which both can be potentiated by stimulation with ISS-ODN. 相似文献
128.
Rick Brouwer Wilma TM Vree Egberts Gerald JD Hengstman Reinout Raijmakers Baziel GM van Engelen Hans Peter Seelig Manfred Renz Rudolf Mierau Ekkehard Genth Ger JM Pruijn Walther J van Venrooij 《Arthritis research & therapy》2001,4(2):1-5
The autoantigenic polymyositis/scleroderma (PM/Scl) complex was recently shown to be the human homologue of the yeast exosome, which is an RNA-processing complex. Our aim was to assess whether, in addition to targeting the known autoantigens PM/Scl-100 and PM/Scl-75, autoantibodies also target recently identified components of the PM/Scl complex. The prevalence of autoantibodies directed to six novel human exosome components (hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p, hCsl4p) was determined in sera from patients with idiopathic inflammatory myopathy (n = 48), scleroderma (n = 11), or the PM/Scl overlap syndrome (n = 10). The sera were analyzed by enzyme-linked immunosorbent assays and western blotting using the affinity-purified recombinant proteins. Our results show that each human exosome component is recognized by autoantibodies. The hRrp4p and hRrp42p components were most frequently targeted. The presence of autoantibodies directed to the novel components of the human exosome was correlated with the presence of the anti-PM/Scl-100 autoantibody in the sera of patients with idiopathic inflammatory myopathy (IIM), as was previously found for the anti-PM/Scl-75 autoantibody. Other clear associations between autoantibody activities were not found. These results further support the conception that the autoimmune response may initially be directed to PM/Scl-100, whereas intermolecular epitope spreading may have caused the autoantibody response directed to the associated components. 相似文献
129.
130.