首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   111篇
  免费   4篇
化学工业   52篇
机械仪表   2篇
建筑科学   4篇
能源动力   1篇
轻工业   17篇
无线电   2篇
一般工业技术   9篇
冶金工业   4篇
自动化技术   24篇
  2023年   4篇
  2022年   12篇
  2021年   11篇
  2020年   1篇
  2019年   11篇
  2018年   2篇
  2017年   3篇
  2016年   3篇
  2015年   5篇
  2014年   4篇
  2013年   8篇
  2012年   5篇
  2011年   7篇
  2010年   1篇
  2009年   7篇
  2008年   6篇
  2007年   3篇
  2006年   2篇
  2005年   2篇
  2004年   2篇
  2002年   1篇
  2001年   1篇
  2000年   2篇
  1999年   1篇
  1998年   3篇
  1997年   2篇
  1987年   1篇
  1986年   1篇
  1985年   1篇
  1984年   1篇
  1982年   1篇
  1981年   1篇
排序方式: 共有115条查询结果,搜索用时 0 毫秒
71.
    
Human serine racemase (hSR) is a pyridoxal-5′-phosphate (PLP)-dependent dimer that catalyzes the formation of D-serine from L-serine, as well as the dehydration of both L- and D-serine to pyruvate and ammonia. As D-serine is a co-agonist of N-methyl-D-aspartate receptors (NMDARs), hSR is a key enzyme in glutamatergic neurotransmission. hSR activity is finely regulated by Mg2+, ATP, post-translational modifications, and the interaction with protein partners. In particular, the C-terminus of murine SR binds the third PDZ domain (PDZ3) of postsynaptic density protein 95 (PSD-95), a member of the membrane-associated guanylate kinase (MAGUK) family involved in the trafficking and localization of glutamate receptors. The structural details of the interaction and the stability of the complex have not been elucidated yet. We evaluated the binding of recombinant human PSD-95 PDZ3 to hSR by glutaraldehyde cross-linking, pull-down assays, isothermal titration calorimetry, nuclear magnetic resonance, and enzymatic assays. Overall, a weak interaction was observed, confirming the binding for the human orthologs but supporting the hypothesis that a third protein partner (i.e., stargazin) is required for the regulation of hSR activity by PSD-95 and to stabilize their interaction.  相似文献   
72.
    
Cyclin-dependent kinase 5 (Cdk5) is an atypical proline-directed serine/threonine protein kinase well-characterized for its role in the central nervous system rather than in the cell cycle. Indeed, its dysregulation has been strongly implicated in the progression of synaptic dysfunction and neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also in the development and progression of a variety of cancers. For this reason, Cdk5 is considered as a promising target for drug design, and the discovery of novel small-molecule Cdk5 inhibitors is of great interest in the medicinal chemistry field. In this context, we employed a machine learning-based virtual screening protocol with subsequent molecular docking, molecular dynamics simulations and binding free energy evaluations. Our virtual screening studies resulted in the identification of two novel Cdk5 inhibitors, highlighting an experimental hit rate of 50% and thus validating the reliability of the in silico workflow. Both identified ligands, compounds CPD1 and CPD4, showed a promising enzyme inhibitory activity and CPD1 also demonstrated a remarkable antiproliferative activity in ovarian and colon cancer cells. These ligands represent a valuable starting point for structure-based hit-optimization studies aimed at identifying new potent Cdk5 inhibitors.  相似文献   
73.
    
Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese.  相似文献   
74.
    
Bone-marrow-mesenchymal-stromal-cells (BMSCs)- and platelet-rich-plasma (PRP)-based therapies have shown potential for treating osteoarthritis (OA). Recently, the combination of these two approaches was proposed, with results that overcame those observed with the separate treatments, indicating a possible role of PRP in ameliorating BMSCs’ regenerative properties. Since a molecular fingerprint of BMSCs cultivated in the presence of PRP is missing, the aim of this study was to characterize the secretome in terms of soluble factors and extracellular-vesicle (EV)-embedded miRNAs from the perspective of tissues, pathways, and molecules which frame OA pathology. One hundred and five soluble factors and one hundred eighty-four EV-miRNAs were identified in the PRP-treated BMSCs’ secretome, respectively. Several soluble factors were related to the migration of OA-related immune cells, suggesting the capacity of BMSCs to attract lympho-, mono-, and granulocytes and modulate their inflammatory status. Accordingly, several EV-miRNAs had an immunomodulating role at both the single-factor and cell level, together with the ability to target OA-characterizing extracellular-matrix-degrading enzymes and cartilage destruction pathways. Overall, anti-inflammatory and protective signals far exceeded inflammation and destruction cues for cartilage, macrophages, and T cells. This study demonstrates that BMSCs cultivated in the presence of PRP release therapeutic molecules and give molecular ground for the use of this combined and innovative therapy for OA treatment.  相似文献   
75.
Reactive oxygen species (ROS) are wieldy accepted as one of the main factors of the aging process. These highly reactive compounds modify nucleic acids, proteins and lipids and affect the functionality of mitochondria in the first case and ultimately of the cell. Any agent or genetic modification that affects ROS production and detoxification can be expected to influence longevity. On the other hand, genetic manipulations leading to increased longevity can be expected to involve cellular changes that affect ROS metabolism. The 66-kDa isoform of the growth factor adaptor Shc (p66Shc) has been recognized as a relevant factor to the oxygen radical theory of aging. The most recent data indicate that p66Shc protein regulates life span in mammals and its phosphorylation on serine 36 is important for the initiation of cell death upon oxidative stress. Moreover, there is strong evidence that apart from aging, p66Shc may be implicated in many oxidative stress-associated pathologies, such as diabetes, mitochondrial and neurodegenerative disorders and tumorigenesis. This article summarizes recent knowledge about the role of p66Shc in aging and senescence and how this protein can influence ROS production and detoxification, focusing on studies performed on skin and skin fibroblasts.  相似文献   
76.
Estimating the selectivity of multidimensional range queries over real valued attributes has significant applications in data exploration and database query optimization. In this paper, we consider the following problem: given a table of d attributes whose domain is the real numbers and a query that specifies a range in each dimension, find a good approximation of the number of records in the table that satisfy the query. The simplest approach to tackle this problem is to assume that the attributes are independent. More accurate estimators try to capture the joint data distribution of the attributes. In databases, such estimators include the construction of multidimensional histograms, random sampling, or the wavelet transform. In statistics, kernel estimation techniques are being used. Many traditional approaches assume that attribute values come from discrete, finite domains, where different values have high frequencies. However, for many novel applications (as in temporal, spatial, and multimedia databases) attribute values come from the infinite domain of real numbers. Consequently, each value appears very infrequently, a characteristic that affects the behavior and effectiveness of the estimator. Moreover, real-life data exhibit attribute correlations that also affect the estimator. We present a new histogram technique that is designed to approximate the density of multidimensional datasets with real attributes. Our technique defines buckets of variable size and allows the buckets to overlap. The size of the cells is based on the local density of the data. The use of overlapping buckets allows a more compact approximation of the data distribution. We also show how to generalize kernel density estimators and how to apply them to the multidimensional query approximation problem. Finally, we compare the accuracy of the proposed techniques with existing techniques using real and synthetic datasets. The experimental results show that the proposed techniques behave more accurately in high dimensionalities than previous approaches.Received: 30 January 2001, Accepted: 9 June 2003, Published online: 4 March 2004Edited by: Y. IoannidisDimitrios Gunopulos: Supported by NSF ITR-0220148, NSF IIS-9907477 CAREER Award, NSF IIS-9984729, and NRDRP.George Kollios: Supported by NSF IIS-0133825 CAREER Award.Vassilis J. Tsotras: Supported by NSF IIS-9907477 and the US Dept. of Defense.  相似文献   
77.
Platinum catalysts supported on ordered mesoporous carbons (OMC) are described. The mesoporous carbon support, CMK3 type, was synthesised as an inverse replica of a SBA-15 silica template. The platinum catalysts (i.e. Pt 20 wt% and Pt 10 wt%, respectively), obtained through a conventional wet impregnation method, have been investigated to determine their structural characteristics and electrochemical behaviour. The electro-catalytic performance towards the oxygen reduction reaction (ORR) was compared to those of commercial Pt/C-Vulcan XTC72R (E-Tek) catalysts with the same Pt wt%, under the same experimental conditions. The two catalyst samples have allowed the effect of the variation of both the Pt to Nafion and Pt to the supporting carbon ratios to be studied. Electrochemical tests have been carried out in three different systems: a catalyst ink deposited on a glassy carbon rotating disk electrode (RDE), a gas diffusion electrode (GDE) in a three-electrode cell with H2SO4 as the electrolyte and a complete PEM single fuel cell. The first results indicate that the OMC performs slightly less well than commercial carbon supports, mainly in the complete fuel cell system. The data from the cell tests indicate a less effective distribution of Nafion on the OMC surface which, probably, decreases the platinum utilisation and the proton conductivity.  相似文献   
78.
79.
80.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号