全文获取类型
收费全文 | 322篇 |
免费 | 18篇 |
专业分类
340篇 |
出版年
2021年 | 1篇 |
2019年 | 2篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 24篇 |
2012年 | 16篇 |
2011年 | 15篇 |
2010年 | 24篇 |
2009年 | 26篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 13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 | 5篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1991年 | 5篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1986年 | 1篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 16篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有340条查询结果,搜索用时 0 毫秒
41.
Susan JM Hoonhorst Wim Timens Leo Koenderman Adèle T Lo Tam Loi Jan-Willem J Lammers H Marike Boezen Antoon JM van Oosterhout Dirkje S Postma Nick HT ten Hacken 《Respiratory research》2014,15(1)
Background
Cigarette smoking is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD). Only a subgroup of smokers develops COPD and it is unclear why these individuals are more susceptible to the detrimental effects of cigarette smoking. The risk to develop COPD is known to be higher in individuals with familial aggregation of COPD. This study aimed to investigate if acute systemic and local immune responses to cigarette smoke differentiate between individuals susceptible or non-susceptible to develop COPD, both at young (18-40 years) and old (40-75 years) age.Methods
All participants smoked three cigarettes in one hour. Changes in inflammatory markers in peripheral blood (at 0 and 3 hours) and in bronchial biopsies (at 0 and 24 hours) were investigated. Acute effects of smoking were analyzed within and between susceptible and non-susceptible individuals, and by multiple regression analysis.Results
Young susceptible individuals showed significantly higher increases in the expression of FcγRII (CD32) in its active forms (A17 and A27) on neutrophils after smoking (p = 0.016 and 0.028 respectively), independently of age, smoking status and expression of the respective markers at baseline. Smoking had no significant effect on mediators in blood or inflammatory cell counts in bronchial biopsies. In the old group, acute effects of smoking were comparable between healthy controls and COPD patients.Conclusions
We show for the first time that COPD susceptibility at young age associates with an increased systemic innate immune response to cigarette smoking. This suggests a role of systemic inflammation in the early induction phase of COPD.Trial registration
Clinicaltrials.gov: NCT00807469Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0121-2) contains supplementary material, which is available to authorized users. 相似文献42.
S Chen AJ de Craen Y Raz E Derhovanessian AC Vossen WG Rudi G Pawelec AB Maier 《Immunity & ageing : I & A》2012,9(1):18-7
ABSTRACT: BACKGROUND: Cytomegalovirus (CMV) infection has been reported to contribute to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, CMV infection has not been evaluated as a possible risk factor for type 2 diabetes. Our aim was to investigate potential associations between CMV seropositivity, CMV IgG antibody level and glucose regulation in the oldest old. RESULTS: CMV seropositive subjects were more likely to have type 2 diabetes (17.2% vs 7.9%, p = 0.016), had a higher level of HbA1c (p = 0.014) and higher non-fasting glucose (p = 0.024) in the oldest olds. These associations remained significant after adjustment for possible confounders. CMV IgG antibody level was not significantly associated with glucose regulation (all p > 0.05). CONCLUSIONS: In the oldest old, CMV seropositivity is significantly associated with various indicators of glucose regulation. This finding suggests that CMV infection might be a risk factor for the development of type 2 diabetes in the elderly. 相似文献
43.
van Wyk L van der Marel J Schuerwegh AJ Schouffoer AA Voskuyl AE Huizinga TW Bianchi DW Scherjon SA 《Arthritis research & therapy》2011,13(6):R183
Introduction
Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma. 相似文献44.
45.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献
46.
L-Lactate dehydrogenase (L-LDH, E.C. 1.1.1.27) is encoded by two or three
loci in all vertebrates examined, with the exception of lampreys, which
have a single LDH locus. Biochemical characterizations of LDH proteins have
suggested that a gene duplication early in vertebrate evolution gave rise
to Ldh-A and Ldh-B and that an additional locus, Ldh-C arose in a number of
lineages more recently. Although some phylogenetic studies of LDH protein
sequences have supported this pattern of gene duplication, others have
contradicted it. In particular, a number of studies have suggested that
Ldh-C represents the earliest divergence among vertebrate LDHs and that it
may have diverged from the other loci well before the origin of
vertebrates. Such hypotheses make explicit statements about the
relationship of vertebrate and invertebrate LDHs, but to date, no closely
related invertebrate LDH sequences have been available for comparison. We
have attempted to provide further data on the timing of gene duplications
leading to multiple vertebrate LDHs by determining the cDNA sequence of the
LDH of the tunicate Styela plicata. Phylogenetic analyses of this and other
LDH sequences provide strong support for the duplications giving rise to
multiple vertebrate LDHs having occurred after vertebrates diverged from
tunicates. The timing of these LDH duplications is consistent with data
from a number of other gene families suggesting widespread gene duplication
near the origin of vertebrates. With respect to the relationships among
vertebrate LDHs, our data are not consistent with previous claims that
Ldh-C represented the earliest divergence. However, the precise
relationships among some of the main lineages of vertebrate LDHs were not
resolved in our analyses.
相似文献
47.
48.
Schilders G Raijmakers R Malmegrim KC Vande Walle L Saelens X Vree Egberts W van Venrooij WJ Vandenabeele P Pruijn GJ 《Arthritis research & therapy》2007,9(1):R12
Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive
systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that
functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly
in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75,
is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75
cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by
caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal
part of the protein at Asp369 (IILD369↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally,
the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed. 相似文献
49.
Judith van Holten Kris Reedquist Pascale Sattonet-Roche Tom JM Smeets Christine Plater-Zyberk Margriet J Vervoordeldonk Paul P Tak 《Arthritis research & therapy》2004,6(3):R239
We investigated the therapeutic potential and mechanism of action of IFN-β protein for the treatment of rheumatoid arthritis
(RA). Collagen-induced arthritis was induced in DBA/1 mice. At the first clinical sign of disease, mice were given daily injections
of recombinant mouse IFN-β or saline for 7 days. Disease progression was monitored by visual clinical scoring and measurement
of paw swelling. Inflammation and joint destruction were assessed histologically 8 days after the onset of arthritis. Proteoglycan
depletion was determined by safranin O staining. Expression of cytokines, receptor activator of NF-κB ligand, and c-Fos was
evaluated immunohistochemically. The IL-1-induced expression of IL-6, IL-8, and granulocyte/macrophage-colony-stimulating
factor (GM-CSF) was studied by ELISA in supernatant of RA and osteoarthritis fibroblast-like synoviocytes incubated with IFN-β.
We also examined the effect of IFN-β on NF-κB activity. IFN-β, at 0.25 μg/injection and higher, significantly reduced disease
severity in two experiments, each using 8–10 mice per treatment group. IFN-β-treated animals displayed significantly less
cartilage and bone destruction than controls, paralleled by a decreased number of positive cells of two gene products required
for osteoclastogenesis, receptor activator of NF-κB ligand and c-Fos. Tumor necrosis factor α and IL-6 expression were significantly
reduced, while IL-10 production was increased after IFN-β treatment. IFN-β reduced expression of IL-6, IL-8, and GM-CSF in
RA and osteoarthritis fibroblast-like synoviocytes, correlating with reduced NF-κB activity. The data support the view that
IFN-β is a potential therapy for RA that might help to diminish both joint inflammation and destruction by cytokine modulation. 相似文献
50.
The anti-PM/Scl autoantibodies are known to characterize a subset of autoimmune patients with myositis, scleroderma (Scl), and the PM/Scl overlap syndrome. The major autoantigens that are recognized by anti-PM/Scl autoantibodies are designated PM/Scl-100 and PM/Scl-75. These autoantigens have been reported to associate into a large complex consisting of 11 to 16 proteins and to play a role in ribosome synthesis. Recently, it was discovered that the PM/Scl complex is the human counterpart of the yeast (Saccharomyces cerevisiae) exosome, which is an RNA-processing complex consisting of 11 3' → 5' exoribonucleases. To date, 10 human exosome components have been identified, although only some of these were studied in more detail. In this review, we discuss some recent advances in the characterization of the PM/Scl complex. 相似文献