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   1703篇
  免费   120篇
  国内免费   128篇
  1951篇
  2024年   6篇
  2023年   57篇
  2022年   46篇
  2021年   91篇
  2020年   77篇
  2019年   98篇
  2018年   79篇
  2017年   79篇
  2016年   60篇
  2015年   56篇
  2014年   82篇
  2013年   121篇
  2012年   56篇
  2011年   87篇
  2010年   45篇
  2009年   80篇
  2008年   75篇
  2007年   102篇
  2006年   87篇
  2005年   73篇
  2004年   52篇
  2003年   60篇
  2002年   44篇
  2001年   21篇
  2000年   23篇
  1999年   38篇
  1998年   20篇
  1997年   21篇
  1996年   23篇
  1995年   20篇
  1994年   14篇
  1993年   16篇
  1992年   6篇
  1991年   14篇
  1990年   8篇
  1989年   8篇
  1988年   5篇
  1987年   6篇
  1986年   7篇
  1985年   7篇
  1984年   14篇
  1983年   8篇
  1982年   6篇
  1981年   4篇
  1980年   12篇
  1979年   12篇
  1978年   6篇
  1975年   5篇
  1974年   4篇
  1973年   4篇
排序方式: 共有1951条查询结果,搜索用时 0 毫秒
991.
This study aims to investigate the impact of consumer familiarity with edible insect food products on purchase intentions and expected liking. Based on persuasion and information processing theories, this study examines the roles of media trust and purchase activism as underlying psychological mechanisms. The findings of this study indicate that consumer familiarity contributes to the formation of media trust. It adds credibility to the media information and consumers can be more motivated to exercise their purchase activism as the edible insect food movement is closely related to social causes like sustainability. Activist motivation, then, changes consumers' behavioral outcomes such as purchase intention and expected liking of edible insect food products.  相似文献   
992.
Marine organisms and micro‐organisms are a source of natural compounds with unique chemical features. These chemical properties are useful for the discovery of new functions and applications of marine natural products (MNPs). To extensively exploit the potential implementations of MNPs, they are gathered in chemical databases that allow their study and screening for applications of biotechnological interest. However, the classification of MNPs is currently poor in generic chemical databases. The present availability of free‐access‐focused MNP databases is scarce and the molecular diversity of these databases is still very low when compared to the paid‐access ones. In this review paper, the current scenario of free‐access MNP databases is presented as well as the hindrances involved in their development, mainly compound dereplication. Examples and opportunities for using freely accessible MNP databases in several important areas of biotechnology are also assessed. The scope of this paper is, as well, to notify the latent potential of these information sources for the discovery and development of new MNPs in biotechnology, and push future efforts to develop a public domain MNP database freely available for the scientific community.  相似文献   
993.
The blood-brain barrier (BBB) consists of differentiated cells integrating in one ensemble to control transport processes between the central nervous system (CNS) and peripheral blood. Molecular organization of BBB affects the extracellular content and cell metabolism in the CNS. Developmental aspects of BBB attract much attention in recent years, and barriergenesis is currently recognized as a very important and complex mechanism of CNS development and maturation. Metabolic control of angiogenesis/barriergenesis may be provided by glucose utilization within the neurovascular unit (NVU). The role of glycolysis in the brain has been reconsidered recently, and it is recognized now not only as a process active in hypoxic conditions, but also as a mechanism affecting signal transduction, synaptic activity, and brain development. There is growing evidence that glycolysis-derived metabolites, particularly, lactate, affect barriergenesis and functioning of BBB. In the brain, lactate produced in astrocytes or endothelial cells can be transported to the extracellular space via monocarboxylate transporters (MCTs), and may act on the adjoining cells via specific lactate receptors. Astrocytes are one of the major sources of lactate production in the brain and significantly contribute to the regulation of BBB development and functioning. Active glycolysis in astrocytes is required for effective support of neuronal activity and angiogenesis, while endothelial cells regulate bioavailability of lactate for brain cells adjusting its bidirectional transport through the BBB. In this article, we review the current knowledge with regard to energy production in endothelial and astroglial cells within the NVU. In addition, we describe lactate-driven mechanisms and action of alternative products of glucose metabolism affecting BBB structural and functional integrity in developing and mature brain.  相似文献   
994.
BackgroundThere is growing interest in the development of cell culture assays that enable the rigidity of the extracellular matrix to be increased. A promising approach is based on three-dimensional collagen type I matrices that are stiffened by cross-linking through non-enzymatic glycation with reducing sugars.MethodsThe present study evaluated the biomechanical changes in the non-enzymatically glycated type I collagen matrices, including collagen organization, the advanced glycation end products formation and stiffness achievement. Gels were glycated with ribose at different concentrations (0, 5, 15, 30 and 240 mM). The viability and the phenotypic changes of primary human lung fibroblasts cultured within the non-enzymatically glycated gels were also evaluated along three consecutive weeks. Statistical tests used for data analyze were Mann–Whitney U, Kruskal Wallis, Student’s t-test, two-way ANOVA, multivariate ANOVA, linear regression test and mixed linear model.ResultsOur findings indicated that the process of collagen glycation increases the stiffness of the matrices and generates advanced glycation end products in a ribose concentration-dependent manner. Furthermore, we identified optimal ribose concentrations and media conditions for cell viability and growth within the glycated matrices. The microenvironment of this collagen based three-dimensional culture induces α-smooth muscle actin and tenascin-C fibroblast protein expression. Finally, a progressive contractile phenotype cell differentiation was associated with the contraction of these gels.ConclusionsThe use of non-enzymatic glycation with a low ribose concentration may provide a suitable model with a mechanic and oxidative modified environment with cells embedded in it, which allowed cell proliferation and induced fibroblast phenotypic changes. Such culture model could be appropriate for investigations of the behavior and phenotypic changes in cells that occur during lung fibrosis as well as for testing different antifibrotic therapies in vitro.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0237-z) contains supplementary material, which is available to authorized users.  相似文献   
995.
The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4, 8-10, 14, 17, 34, and 40 demonstrated urease inhibition in the range of IC50 = 4.4 ± 0.21–115.6 ± 2.13 μM, as compared to standard thiourea (IC50 = 21.3 ± 1.3 μM). Especially, compound 17 (IC50 = 4.4 ± 0.21 μM) was found to be five-fold more potent than the standard. Kinetic studies were also performed on compound 17 in order to identify the mechanism of inhibition. Kinetic studies revealed that compound 17 is a competitive inhibitor. Antiglycation activity was evaluated using glycation of bovine serum albumin by methylglyoxal in vitro. Compounds 2, 11-13, 16, 17, 1922, 35, 37, and 42 showed good to moderate antiglycation activities with IC50 values of 333.63–919.72 μM, as compared to the standard rutin (IC50 = 294.46 ± 1.5 μM). Results of both assays showed that the compounds with urease inhibitory activity did not show any antiglycation potential, and vice versa. Only compound 17 showed dual inhibition potential. All compounds were also evaluated for cytotoxicity. Compounds 17, 19, and 37 showed a weak toxicity towards 3 T3 mouse fibroblast cell line. All other compounds were found to be non-cytotoxic. Urease inhibition is an approach to treat infections caused by ureolytic bacteria whereas inhibition of glycation of proteins is a strategy to avoid late diabetic complications. Therefore, these compounds may serve as leads for further research.  相似文献   
996.
Nowadays, food, cosmetic, environmental and pharmaceutical fields are searching for alternative processes to obtain their major products in a more sustainable way. This fact is related to the increasing demand from the consumer market for natural products to substitute synthetic additives. Industrial biotechnology appears as a promising area for this purpose; however, the success of its application is highly dependent of the availability of a suitable microorganism. To overcome this drawback, the isolation of microorganisms from diverse sources, including fermented food, adverse environments, contaminated samples or agro-industrial wastes is an important approach that can provide a more adaptable strain able to be used as biocatalyst and that exhibit resistance to industrial conditions and high yields/productivities in biotechnological production of natural compounds. The aim of this review is to provide a solid set of information on the state of the art of isolation and screening studies for obtaining novel biocatalysts able to produce natural compounds, focusing in aromas, biosurfactants, polysaccharides and microbial oils.  相似文献   
997.
Peptides, biologically occurring oligomers of amino acids linked by amide bonds, are essential for living organisms. Many peptides isolated as natural products have biological functions such as antimicrobial, antivirus and insecticidal activities. Peptides often possess structural features or modifications not found in proteins, including the presence of nonproteinogenic amino acids, macrocyclic ring formation, heterocyclization, N-methylation and decoration by sugars or acyl groups. Nature employs various strategies to increase the structural diversity of peptides. Enzymes that modify peptides to yield mature natural products are of great interest for discovering new enzyme chemistry and are important for medicinal chemistry applications. We have discovered novel peptide modifying enzymes and have identified: (i) a new class of amide bond forming-enzymes; (ii) a pathway to biosynthesize a carbonylmethylene-containing pseudodipeptide structure; and (iii) two distinct peptide epimerases. In this review, an overview of our findings on peptide modifying enzymes is presented.  相似文献   
998.
A variety of degradation products are produced upon pretreatment of lignocellulosic biomass with dilute acid. To date, the complexity of these samples has significantly limited the scope of efforts to perform summative analyses of degradation products. Qualitative and quantitative interrogation of hydrolysates is also paramount to identifying potential correlations between pretreatment chemistry and microbial inhibition in downstream bioconversion processes. A recently developed reversed-phase high performance liquid chromatography technique with UV detection has been applied to perform quantitative assessments of a variety of hydrolysate components as a function of pretreatment time and temperature. Correlations of product concentrations to the pretreatment severity function indicate differing responses of various compounds to the kinetic influences of temperature and reaction time. Of the compounds measured, four demonstrated initial accumulation rates were sufficiently linear over the time period tested to enable determination of activation energy E(a). All four compounds appear to demonstrate higher E(a) than that assumed in the commonly applied severity function. Overall accumulation trends for most compounds indicated similar under-estimation of apparent activation energy by the severity function. Biotechnol. Bioeng. 2007;98: 1135-1145. (c) 2007 Wiley Periodicals, Inc.  相似文献   
999.
Chen Q  Du Y 《Carbohydrate research》2007,342(11):1405-1411
A total synthesis of the 12-membered ring natural macrolide, sporiolide B, was achieved from D-glucal in 17 steps with 4.8% overall yield. The required stereochemical configuration at C-3 and C-5 in sporiolide B was easily introduced by applying a Mitsunobu reaction on the chiral template D-glucal. Yamaguchi esterification and ring closing metathesis greatly improved the access to the target compound.  相似文献   
1000.
Catabolic products from anaerobic fermentation processes are potentially of industrial interest. The volatile fatty acids and alcohols produced can be used as building blocks in chemical processes or applied directly as substrates in a mixed culture process to produce bioplastics. Development of such applications requires a predictable and controllable product spectrum of the fermentation process. The aim of the research described in this paper was (i) to investigate the product spectrum of an open mixed culture fermentation (MCF) process as a function of the pH, using glucose as substrate, and (ii) to relate the product spectrum obtained to generalized biochemical and thermodynamic considerations. A chemostat was operated under carbon and energy limitation in order to investigate the pH effect on the product spectrum in a MCF process. A transition from CO(2)/H(2) production at lower pH values to formate production at higher pH values was observed. The ratio of CO(2)/H(2) versus formate production was found to be related to the thermodynamics of formate dehydrogenation to CO(2)/H(2). This transition was associated with a shift in the catabolic products, from butyrate and acetate to ethanol and acetate, likely due to a decrease in the oxidation state of the electron carriers in the cell. The product spectrum of the MCF process as a function of the pH could largely be explained using general biochemical considerations.  相似文献   
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