全文获取类型
收费全文 | 107篇 |
免费 | 2篇 |
专业分类
109篇 |
出版年
2021年 | 2篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 8篇 |
2013年 | 8篇 |
2012年 | 3篇 |
2011年 | 11篇 |
2010年 | 11篇 |
2009年 | 10篇 |
2008年 | 8篇 |
2007年 | 5篇 |
2006年 | 3篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有109条查询结果,搜索用时 10 毫秒
101.
102.
Bjorn?WH?van Heumen Hennie?MJ?Roelofs René?HM?te Morsche Fokko?M?Nagengast Wilbert?HM?PetersEmail author 《Orphanet journal of rare diseases》2013,8(1):181
Background
Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.Methods
Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.Results
mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.Conclusions
Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.Trial registration
http://ClinicalTrials.gov number NCT00808743103.
Jennifer H Humphreys Jessica AB van Nies Jackie Chipping Tarnya Marshall Annette HM van der Helm-van Mil Deborah PM Symmons Suzanne MM Verstappen 《Arthritis research & therapy》2014,16(6)
Introduction
This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).Methods
Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.Results
A total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15).Conclusions
Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0483-3) contains supplementary material, which is available to authorized users. 相似文献104.
Hui-Chen Wu Qiao Wang Wendy K Chung Irene L Andrulis Mary B Daly Esther M John Theresa HM Keegan Julia Knight Angela R Bradbury Maya A Kappil Irina Gurvich Regina M Santella Mary Beth Terry 《Epigenetics》2014,9(7):929-933
Many epidemiologic studies of environmental exposures and disease susceptibility measure DNA methylation in white blood cells (WBC). Some studies are also starting to use saliva DNA as it is usually more readily available in large epidemiologic studies. However, little is known about the correlation of methylation between WBC and saliva DNA. We examined DNA methylation in three repetitive elements, Sat2, Alu, and LINE-1, and in four CpG sites, including AHRR (cg23576855, cg05575921), cg05951221 at 2q37.1, and cg11924019 at CYP1A1, in 57 girls aged 6–15 years with blood and saliva collected on the same day. We measured all DNA methylation markers by bisulfite-pyrosequencing, except for Sat2 and Alu, which were measured by the MethyLight assay. Methylation levels measured in saliva DNA were lower than those in WBC DNA, with differences ranging from 2.8% for Alu to 14.1% for cg05575921. Methylation levels for the three repetitive elements measured in saliva DNA were all positively correlated with those in WBC DNA. However, there was a wide range in the Spearman correlations, with the smallest correlation found for Alu (0.24) and the strongest correlation found for LINE-1 (0.73). Spearman correlations for cg05575921, cg05951221, and cg11924019 were 0.33, 0.42, and 0.79, respectively. If these findings are replicated in larger studies, they suggest that, for selected methylation markers (e.g., LINE-1), methylation levels may be highly correlated between blood and saliva, while for others methylation markers, the levels may be more tissue specific. Thus, in studies that differ by DNA source, each interrogated site should be separately examined in order to evaluate the correlation in DNA methylation levels across DNA sources. 相似文献
105.
With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with
persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period,
or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first
is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced
state of minimal disease activity are not well defined. These definitions of remission refer to different disease states;
therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs. 相似文献
106.
107.
Background
Every year many dogs in Sweden are bitten by Vipera berus, the only venomous viper in Sweden. This prospective study investigated clinical signs, some biochemical parameters, treatment, and progress of disease after snakebite in 53 dogs. Effects of treatment with and without glucocorticoids were evaluated. 相似文献108.
Easier detection of invertebrate "identification-key characters" with light of different wavelengths
Evolutionary arms-races between avian brood parasites and their hosts have typically resulted in some spectacular adaptations, namely remarkable host ability to recognize and reject alien eggs and, in turn, sophisticated parasite egg mimicry. In a striking contrast to hosts sometimes rejecting even highly mimetic eggs, the same species typically fail to discriminate against highly dissimilar parasite chicks. Understanding of this enigma is still hampered by the rarity of empirical tests - and consequently evidence - for chick discrimination. Recent work on Australian host-parasite systems (Gerygone hosts vs. Chalcites parasites), increased not only the diversity of hosts showing chick discrimination, but also discovered an entirely novel host behavioural adaptation. The hosts do not desert parasite chicks (as in all previously reported empirical work) but physically remove living parasites from their nests. Here, I briefly discuss these exciting findings and put them in the context of recent empirical and theoretical work on parasite chick discrimination. Finally, I review factors responsible for a relatively slow progress in this research area and suggest most promising avenues for future research. 相似文献
109.
Jaruwan Kampa Karl Ståhl Lena HM Renström Stefan Alenius 《Acta veterinaria Scandinavica》2007,49(1):7