全文获取类型
收费全文 | 64篇 |
免费 | 10篇 |
国内免费 | 1篇 |
出版年
2019年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2013年 | 4篇 |
2012年 | 2篇 |
2011年 | 1篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 7篇 |
2007年 | 3篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 3篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有75条查询结果,搜索用时 15 毫秒
41.
Summary . Missing data, measurement error, and misclassification are three important problems in many research fields, such as epidemiological studies. It is well known that missing data and measurement error in covariates may lead to biased estimation. Misclassification may be considered as a special type of measurement error, for categorical data. Nevertheless, we treat misclassification as a different problem from measurement error because statistical models for them are different. Indeed, in the literature, methods for these three problems were generally proposed separately given that statistical modeling for them are very different. The problem is more challenging in a longitudinal study with nonignorable missing data. In this article, we consider estimation in generalized linear models under these three incomplete data models. We propose a general approach based on expected estimating equations (EEEs) to solve these three incomplete data problems in a unified fashion. This EEE approach can be easily implemented and its asymptotic covariance can be obtained by sandwich estimation. Intensive simulation studies are performed under various incomplete data settings. The proposed method is applied to a longitudinal study of oral bone density in relation to body bone density. 相似文献
42.
Jigme M Sethi Augustine MK Choi William J Calhoun Bill T Ameredes 《Respiratory research》2008,9(1):45
Background
Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study.Methods
Expired NO (ENO) and CO (ECO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10-/-, A/J, MKK3-/-, JNK1-/-, NOS-2-/- and NOS-3-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. ENO and ECO were also measured in C57Bl6 and IL-10-/- mice, ages 8–58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing.Results
ENO was significantly elevated in naïve IL-10-/- (9–14 ppb) and NOS-2-/- (16 ppb) mice as compared to others (average: 5–8 ppb), whereas ECO was significantly higher in naïve A/J, NOS-3-/- (3–4 ppm), and MKK3-/- (4–5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10-/-, JNK1-/-, NOS-2-/-, and NOS-3-/- mice were decreased, whereas they were greater for A/J and MKK3-/- mice. SMTC significantly decreased ENO by ~30%, but did not change AR in NOS-2-/- mice. SnPP reduced ECO in C57Bl6 and IL-10-/- mice, and increased AR in NOS-2-/- mice. ENO decreased as a function of age in IL-10-/- mice, remaining unchanged in C57Bl6 mice.Conclusion
These results are consistent with the ideas that: 1) ENO is associated with mouse strain and knockout differences in NO production and AR, 2) alterations of ENO and ECO can be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway. 相似文献43.
Biomarkers aid the study of osteoarthritis (OA) in a number of different ways. In this article we summarise briefly their
multiple uses and reflect on how the study reported in a previous edition of Arthritis Research & Therapy should promote further investigation of cartilage oligomeric matrix protein (COMP). COMP is foremost among hitherto investigated
biomarkers and is most consistently shown to predict knee OA progression. Precisely what role it plays in OA pathogenesis
remains unclear and elucidating this may be key to defining, and then targeting, the cellular pathways involved in OA. 相似文献
44.
Khajeddin SJ Akbari M Karimzadeh HR Eghbal MK 《植物生态学报》2008,32(2):328-335
Aims Desertification results in ecological and biological diminution of the earth, and can happen naturally or cause by anthropogenic activities. This process especially affects arid and semi-arid regions, such as the Isfahan region, where the spread of desertification is reaching critical proportions. The aim of this study is to use remotely sensed data to review the trend of desertification in the northern of Isfahan, Iran. Methods Multi-temporal images were employed to evaluate the trend of desertification, specifically the TM and ETM+ data of September, 1990 and September, 2001. Geometric and radiometric corrections were applied to each image prior to image processing and supervised classification, and vegetation indices were applied to produce a land use map of each image in nine classes. The land use classification s in the two map images were compared and changes between land use classes were detected over the 11 year period using a fuzzy and post-classification technique. Important findings The maps and their comparison with false color composite images showed the differences efficiently. With the fuzzy and post-classification method the land use changes were sited on the map. Fuzzy confirmed 53% changed area and 47% unchanged areas in the study region. The results verify the desertification expansion in the study areas. Because of poor land management, agricultural lands converted to desert and abandoned areas, and some marginal pasture lands had to be changed to agricultural land which are desertification spreading according to United Nations Conference on Desertification (UNCOD). Also farmland and pastures have been converted to urban and industrial areas, and the rangelands have been spoiled due to opencast mine excavations. With the mine margins eroding as well as their debris accumulating on the pasture lands, desertification has become worse. Three areas of less-elevated mountains have remained unchanged. This study confirmed that the anthropogenic activities accelerated the desertification process and severely endangered the remaining areas. 相似文献
45.
Background
There are two different theories about the development of the genetic code. Woese suggested that it was developed in connection with the amino acid repertoire, while Crick argued that any connection between codons and amino acids is only the result of an "accident". This question is fundamental to understand the nature of specific protein-nucleic acid interactions. 相似文献46.
Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal PINK1‐dependent phosphorylation and activation
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Agne Kazlauskaite R Julio Martínez‐Torres Scott Wilkie Atul Kumar Julien Peltier Alba Gonzalez Clare Johnson Jinwei Zhang Anthony G Hope Mark Peggie Matthias Trost Daan MF van Aalten Dario R Alessi Alan R Prescott Axel Knebel Helen Walden Miratul MK Muqit 《EMBO reports》2015,16(8):939-954
Mutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser65)—which lies within its ubiquitin‐like domain (Ubl)—and indirectly through phosphorylation of ubiquitin at Ser65. How Ser65‐phosphorylated ubiquitin (ubiquitinPhospho‐Ser65) contributes to Parkin activation is currently unknown. Here, we demonstrate that ubiquitinPhospho‐Ser65 binding to Parkin dramatically increases the rate and stoichiometry of Parkin phosphorylation at Ser65 by PINK1 in vitro. Analysis of the Parkin structure, corroborated by site‐directed mutagenesis, shows that the conserved His302 and Lys151 residues play a critical role in binding of ubiquitinPhospho‐Ser65, thereby promoting Parkin Ser65 phosphorylation and activation of its E3 ligase activity in vitro. Mutation of His302 markedly inhibits Parkin Ser65 phosphorylation at the mitochondria, which is associated with a marked reduction in its E3 ligase activity following mitochondrial depolarisation. We show that the binding of ubiquitinPhospho‐Ser65 to Parkin disrupts the interaction between the Ubl domain and C‐terminal region, thereby increasing the accessibility of Parkin Ser65. Finally, purified Parkin maximally phosphorylated at Ser65 in vitro cannot be further activated by the addition of ubiquitinPhospho‐Ser65. Our results thus suggest that a major role of ubiquitinPhospho‐Ser65 is to promote PINK1‐mediated phosphorylation of Parkin at Ser65, leading to maximal activation of Parkin E3 ligase activity. His302 and Lys151 are likely to line a phospho‐Ser65‐binding pocket on the surface of Parkin that is critical for the ubiquitinPhospho‐Ser65 interaction. This study provides new mechanistic insights into Parkin activation by ubiquitinPhospho‐Ser65, which could aid in the development of Parkin activators that mimic the effect of ubiquitinPhospho‐Ser65. 相似文献
47.
在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 … 总被引:1,自引:0,他引:1
根据22个等位酶位点遗传变异,探讨了韩国境内委陵菜(Potentilla fragarioides L.var.sprengeliana)的遗传多样性和种群结构。酶位点的多态位点百分比为59.1%。种和种群水平上的遗传多样性比较高,分别为Hes=0.210,Hep=0.199;而种群的分化水平则相对较低(GST=0.074)。19个种群中随机交配的偏差为FIS=0.331。每代迁移数的间接估计 相似文献
48.
Recent reports suggest that evolving large-scale networks exhibit “explosive percolation”: a large fraction of nodes suddenly becomes connected when sufficiently many links have formed in a network. This phase transition has been shown to be continuous (second-order) for most random network formation processes, including classical mean-field random networks and their modifications. We study a related yet different phenomenon referred to as dense percolation, which occurs when a network is already connected, but a large group of nodes must be dense enough, i.e., have at least a certain minimum required percentage of possible links, to form a “highly connected” cluster. Such clusters have been considered in various contexts, including the recently introduced network modularity principle in biological networks. We prove that, contrary to the traditionally defined percolation transition, dense percolation transition is discontinuous (first-order) under the classical mean-field network formation process (with no modifications); therefore, there is not only quantitative, but also qualitative difference between regular and dense percolation transitions. Moreover, the size of the largest dense (highly connected) cluster in a mean-field random network is explicitly characterized by rigorously proven tight asymptotic bounds, which turn out to naturally extend the previously derived formula for the size of the largest clique (a cluster with all possible links) in such a network. We also briefly discuss possible implications of the obtained mathematical results on studying first-order phase transitions in real-world linked systems. 相似文献
49.
P Zhu B MK Tong R Wang J P Chen S Foo H C Chong X L Wang G Y Ang S Chiba N S Tan 《Cell death & disease》2013,4(3):e552
Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2−:H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable. 相似文献
50.