全文获取类型
收费全文 | 63篇 |
免费 | 1篇 |
出版年
2021年 | 1篇 |
2014年 | 1篇 |
2013年 | 7篇 |
2012年 | 1篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2008年 | 2篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有64条查询结果,搜索用时 18 毫秒
31.
Joana Louren?o Simone Pacioni Nelson Rebola Geeske M. van Woerden Silvia Marinelli David DiGregorio Alberto Bacci 《PLoS biology》2014,12(7)
In the neocortex, the coexistence of temporally locked excitation and inhibition governs complex network activity underlying cognitive functions, and is believed to be altered in several brain diseases. Here we show that this equilibrium can be unlocked by increased activity of layer 5 pyramidal neurons of the mouse neocortex. Somatic depolarization or short bursts of action potentials of layer 5 pyramidal neurons induced a selective long-term potentiation of GABAergic synapses (LTPi) without affecting glutamatergic inputs. Remarkably, LTPi was selective for perisomatic inhibition from parvalbumin basket cells, leaving dendritic inhibition intact. It relied on retrograde signaling of nitric oxide, which persistently altered presynaptic GABA release and diffused to inhibitory synapses impinging on adjacent pyramidal neurons. LTPi reduced the time window of synaptic summation and increased the temporal precision of spike generation. Thus, increases in single cortical pyramidal neuron activity can induce an interneuron-selective GABAergic plasticity effectively altering the computation of temporally coded information. 相似文献
32.
Partial characterization of diphtheria toxin and its subunits 总被引:8,自引:0,他引:8
33.
Speetjens FM de Bruin EC Morreau H Zeestraten EC Putter H van Krieken JH van Buren MM van Velzen M Dekker-Ensink NG van de Velde CJ Kuppen PJ 《Cancer immunology, immunotherapy : CII》2008,57(5):601-609
Purpose To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal
carcinomas.
Experimental design Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical
staining with two antibodies (HCA2 and HC10).
Results Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with ≤50%
of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found
between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an
independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression
had no effect on cancer-specific survival or recurrence-free survival.
Conclusions Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports
on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors,
having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors
are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As
rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates
patient’s prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of
HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed.
Frank M. Speetjens and Elza C. de Bruin contributed equally to this work.
Cornelis J.H. van de Velde is the Chairperson of the Total Mesorectal Excision Trial. 相似文献
34.
Bacillus species are valuable producers of industrial enzymes and biopharmaceuticals, because they can secrete large quantities of high-quality proteins directly into the growth medium. This requires the concerted action of quality control factors, such as folding catalysts and 'cleaning proteases'. The expression of two important cleaning proteases, HtrA and HtrB, of Bacillus subtilis is controlled by the CssRS two-component regulatory system. The induced CssRS-dependent expression of htrA and htrB has been defined as a protein secretion stress response, because it can be triggered by high-level production of secreted alpha-amylases. It was not known whether translocation of these alpha-amylases across the membrane is required to trigger a secretion stress response or whether other secretory proteins can also activate this response. These studies show for the first time that the CssRS-dependent response is a general secretion stress response which can be triggered by both homologous and heterologous secretory proteins. As demonstrated by high-level production of a nontranslocated variant of the alpha-amylase, AmyQ, membrane translocation of secretory proteins is required to elicit this general protein secretion stress response. Studies with two other secretory reporter proteins, lipase A of B. subtilis and human interleukin-3, show that the intensity of the protein secretion stress response only partly reflects the production levels of the respective proteins. Importantly, degradation of human interleukin-3 by extracellular proteases has a major impact on the production level, but only a minor effect on the intensity of the secretion stress response. 相似文献
35.
36.
Gülmisal Güder Susanne Brenner Christiane E Angermann Georg Ertl Matthias Held Alfred P Sachs Jan-Willem Lammers Pieter Zanen Arno W Hoes Stefan St?rk Frans H Rutten 《Respiratory research》2012,13(1):13
Background
The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.Methods
In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner''s diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.Results
Compared to the expert panel diagnosis, ''GOLD-COPD'' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.Conclusions
GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice. 相似文献37.
38.
Onno M Mets Michael Schmidt Constantinus F Buckens Martijn J Gondrie Ivana Isgum Matthijs Oudkerk Rozemarijn Vliegenthart Harry J de Koning Carlijn M van der Aalst Mathias Prokop Jan-Willem J Lammers Pieter Zanen Firdaus A Mohamed Hoesein Willem PThM Mali Bram van Ginneken Eva M van Rikxoort Pim A de Jong 《Respiratory research》2013,14(1):59
Background
Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans.Methods
Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques.Results
Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%. However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data.Conclusion
Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy. Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting. 相似文献39.
Firdaus A. A. Mohamed Hoesein Pim A. de Jong Jan-Willem J. Lammers Willem PThM Mali Michael Schmidt Harry J. de Koning Carlijn van der Aalst Matthijs Oudkerk Rozemarijn Vliegenthart Bram van Ginneken Eva M. van Rikxoort Pieter Zanen 《PloS one》2013,8(6)
Background
There is increasing evidence that structural lung changes may be present before the occurrence of airflow limitation as assessed by spirometry. This study investigated the prevalence of computed tomography (CT) quantified emphysema, airway wall thickening and gas trapping according to classification of airflow limitation (FEV1/FVC <70% and/or < the lower limit of normal (LLN)) in (heavy) smokers.Methods
A total number of 1,140 male former and current smokers participating in a lung cancer screenings trial (NELSON) were included and underwent chest CT scanning and spirometry. Emphysema was quantified by the 15th percentile, air way wall thickening by the square root of wall area for a theoretical airway with 10mm lumen perimeter (Pi10) and gas trapping by the mean lung density expiratory/inspiratory (E/I)-ratio. Participants were classified by entry FEV1/FVC: group 1>70%; group 2<70% but >LLN; and group 3<LLN. 32 restricted subjects, i.e. FEV1/FVC >70% but FEV1 <80% predicted, were excluded. Multivariate regression analysis correcting for covariates was used to asses the extent of emphysema, airway wall thickening and gas trapping according to three groups of airflow limitation.Results
Mean (standard deviation) age was 62.5 (5.2) years and packyears smoked was 41.0 (18.0). Group 2 subjects when compared to group 1 had a significantly lower 15th percentile, −920.6 HU versus −912.2 HU; a higher Pi10, 2.87 mm versus 2.57 mm; and a higher E/I-ratio, 88.6% versus 85.6% (all p<0.001).Conclusion
Subjects with an FEV1/FVC<70%, but above the LLN, have a significant greater degree of structural lung changes on CT compared to subjects without airflow limitation. 相似文献40.