全文获取类型
收费全文 | 211篇 |
免费 | 24篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 18篇 |
2012年 | 17篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 15篇 |
2008年 | 13篇 |
2007年 | 10篇 |
2006年 | 12篇 |
2005年 | 8篇 |
2004年 | 6篇 |
2003年 | 6篇 |
2002年 | 3篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 4篇 |
1998年 | 12篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有235条查询结果,搜索用时 15 毫秒
61.
Corry-Anke Brandsma Machteld N Hylkema Marie Geerlings Wouter H van Geffen Dirkje S Postma Wim Timens Huib AM Kerstjens 《Respiratory research》2009,10(1):108
There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD. B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients. Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions. We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens). Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells. Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung. The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells. Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD. 相似文献
62.
A Luquita L Urli MJ Svetaz AM Gennaro ME Giorgetti G Pistone R Volpintesta S Palatnik M Rasia 《Journal of biomedical science》2010,17(1):8
Background
Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology. 相似文献63.
Arianna Tavanti Lambert AM Hensgens Selene Mogavero László Majoros Sonia Senesi Mario Campa 《BMC microbiology》2010,10(1):203
Background
Candida parapsilosis is known to show limited genetic variability, despite different karyotypes and phenotypes have been described. To further investigate this aspect, a collection of 62 sensu strictu C. parapsilosis independent isolates from 4 geographic regions (Italy, n = 19; New Zealand, n = 15; Argentina, n = 14; and Hungary, n = 14) and different body sites (superficial and deep seated) were analysed for their genetic and phenotypic traits. Amplification fragment length polymorphism (AFLP) analysis was used to confirm species identification and to evaluate intraspecific genetic variability. Phenotypic characterisation included clinically relevant traits, such as drug susceptibility, in vitro biofilm formation and aspartyl protease secretion. 相似文献64.
Corry-Anke Brandsma Wim Timens Marie Geerlings Henrike Jekel Dirkje S Postma Machteld N Hylkema Huib AM Kerstjens 《BMC pulmonary medicine》2010,10(1):1-10
Background
Despite recommendations for outpatient management, low risk patients with lower respiratory tract infections (LRTIs) are often hospitalized. This survey analyzed perceptions of physicians, nurses, patients and relatives about feasibility of outpatient management and required duration of hospital stay.Methods
We performed a prospective, observational questionnaire survey in hospitalized patients with LRTI as part of a multicenter trial. Treating physicians and nurses, patients and their relatives were asked on admission and before discharge about feasibility of outpatient treatment over 5 dimensions (medical, nursing, organizational factors, and patients' and relatives' preferences) using continuous scales.Results
On admission, 12.6% of physicians, 15.1% of nurses, 18.0% of patients and 5.2% of relatives believed that outpatient treatment would be possible. Before hospital discharge, 31.1% of physicians, 32.2% of nurses, 11.6% of patients and 4.1% of relatives thought that earlier discharge would have been feasible. Medical factors were the most frequently perceived motives for inpatient management. These perceptions were similar in all LRTI subgroups and independent of disease severity and associated expected mortality risks as assessed by the Pneumonia Severity Index (PSI).Conclusion
Independent of type and severity of respiratory tract infection, the misperceived high severity and expected mortality and morbidity were the predominant reasons why treating physicians, nurses, patients and their relatives unanimously believed that inpatient management was necessary. Better assessment and communication about true expected medical risks might contribute to a pathway to shorten in-hospital days and to introduce a more risk-targeted and individually tailored allocation of health-care resources.Trial Registration
NCT00350987 相似文献65.
66.
Background
In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. 相似文献67.
68.
Catimel B; Scott AM; Lee FT; Hanai N; Ritter G; Welt S; Old LJ; Burgess AW; Nice EC 《Glycobiology》1998,8(9):927-938
We describe a novel immobilization technique to investigate interactions
between immobilized gangliosides (GD3, GM1, and GM2) and their respective
antibodies, antibody fragments, or binding partners using an optical
biosensor. Immobilization was performed by direct injection onto a
carboxymethyldextran sensor chip and did not require derivatization of the
sensor surface or the ganglioside. The ganglioside appeared to bind to the
sensor surface by hydrophobic interaction, leaving the carbohydrate epitope
available for antibody or, in the case of GM1, cholera toxin binding. The
carboxyl group of the dextran chains on the sensor surface did not appear
to be involved in the immobilization as evidenced by equivalent levels of
immobilization following conversion of the carboxyl groups into acyl amino
esters, but rather the dextran layer provided a hydrophilic coverage of the
sensor chip which was essential to prevent nonspecific binding. This
technique gave better reactivity and specificity for anti- ganglioside
monoclonal antibodies (anti-GD3: KM871, KM641, R24; and anti-GM2: KM966)
than immobilization by hydrophobic interaction onto a gold sensor surface
or photoactivated cross-linking onto carboxymethydextran. This rapid
immobilization procedure has facilitated detailed kinetic analysis of
ganglioside/antibody interactions, with the surface remaining viable for a
large number of cycles (>125). Kinetic constants were determined from
the biosensor data using linear regression, nonlinear least squares and
equilibrium analysis. The values of kd, ka, and KAobtained by nonlinear
analysis (KAKM871 = 1.05, KM641 = 1.66, R24 = 0.14, and KM966 = 0.65 x
10(7) M- 1) were essentially independent of concentration and showed good
agreement with data obtained by other analytical methods.
相似文献
69.
Influence of a natural and a synthetic inhibitor of factor XIIIa on fibrin clot rheology 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
We investigated the origins of greater clot rigidity associated with FXIIIa-dependent cross-linking. Fibrin clots were examined in which cross-linking was controlled through the use of two inhibitors: a highly specific active-center-directed synthetic inhibitor of FXIIIa, 1,3-dimethyl-4,5-diphenyl-2[2(oxopropyl)thio]imidazolium trifluoromethylsulfonate, and a patient-derived immunoglobulin directed mainly against the thrombin-activated catalytic A subunits of thrombin-activated FXIII. Cross-linked fibrin chains were identified and quantified by one- and two-dimensional gel electrophoresis and immunostaining with antibodies specific for the alpha- and gamma-chains of fibrin. Gamma-dimers, gamma-multimers, alpha(n)-polymers, and alpha(p)gamma(q)-hybrids were detected. The synthetic inhibitor was highly effective in preventing the production of all cross-linked species. In contrast, the autoimmune antibody of the patient caused primarily an inhibition of alpha-chain cross-linking. Clot rigidities (storage moduli, G') were measured with a cone and plate rheometer and correlated with the distributions of the various cross-linked species found in the clots. Our findings indicate that the FXIIIa-induced dimeric cross-linking of gamma-chains by itself is not sufficient to stiffen the fibrin networks. Instead, the augmentation of clot rigidity was more strongly correlated with the formation of gamma-multimers, alpha(n)-polymers, and alpha(p)gamma(q)-hybrid cross-links. A mechanism is proposed to explain how these cross-linked species may enhance clot rigidity. 相似文献
70.
Two isozymes of laccase were obtained from an induced liquid culture of Marasmius quercophilus with p-hydroxybenzoic acid as the inducer. Both the constitutive and the induced isozyme have a molecular mass of 60 kDa as determined by polyacrylamide gel electrophoresis. Using isoelectric focusing, we found three isozymes with the constitutive enzyme (pI 4, 4.2, 4.4) and four of the induced form (pI 4.75, 4.85, 4.95, 5.1). We observed certain differences between these two isozymes; the specific activity of the induced isozyme was twice as high, and two optimum pH levels (5 and 6) were observed with the induced isozyme (only one, pH 5, for the constitutive isozyme). However, both of these enzymes have the same thermal stability and the same temperature for their highest activity (80 degrees C). Furthermore, the reactivity of both these enzymes with aromatic compounds was similar. The use of mediators extended the oxidized substrate range of the laccases studied. Various products of degradation were observed, depending on the mediator used. When laccase was used alone, the decrease of the signal corresponding to the aromatic cycle, without any formations of other peaks at different wavelengths, suggested polymerisation of aromatic compounds. 相似文献