全文获取类型
收费全文 | 274篇 |
免费 | 30篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 8篇 |
2013年 | 15篇 |
2012年 | 23篇 |
2011年 | 26篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 18篇 |
2007年 | 16篇 |
2006年 | 11篇 |
2005年 | 7篇 |
2004年 | 15篇 |
2003年 | 13篇 |
2002年 | 9篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 2篇 |
排序方式: 共有305条查询结果,搜索用时 281 毫秒
151.
Vijayakumar Subramaniyan Reetha Sekar Arulmozhi Praveenkumar Rajalakshmi Selvam 《Quantitative Biology.》2019,7(4):302
Background: Hepatitis B virus (HBV) has affected over 300 million people worldwide which causes to induce mostly liver disease and liver cancer. It is a member of the family Hepadnaviridae which is a small DNA virus with unusual characters like retroviruses. Generally, hepatoprotective drugs provoke some side effects in human beings. For the reason, this study aims to identify alternative drug molecules from the natural source of medicinal plants with smaller quantity of side effects than those conventional drugs in treating HBV. Methods: We developed computational methods for calculating drug and target binding resemblance using the Maestro v10.2 of Schrodinger suite. The target and ligand molecules were obtained from recognized databases. Ligand molecules of 40 phytoconstituents were retrieved from variety of plants after we executed crucial analyses such as molecular docking and absorption, distribution, metabolism, and excretion (ADME) analysis.Results: In the docking analysis, the natural analogues repandusinic acid showed better docking scores of –14.768 with good binding contacts. The remaining bioactive molecules corilagin, furosin, nirurin, iso-quercetin and gallocatechin also showed better docking scores.Conclusion: This computational analysis reveals that repandusinic acid is a suitable drug candidate for HBV. Therefore, we recommend that this analogue is suitable in further exploration using in vitro studies. 相似文献
152.
153.
Defining the spectrum of alleles that contribute to blood lipid concentrations in humans 总被引:1,自引:0,他引:1
PURPOSE OF REVIEW: Recently, genome-wide genetic screening of common DNA sequence variants has proven a successful approach to identify novel genetic contributors to complex traits. This review summarizes recent genome-wide association studies for lipid phenotypes, and evaluates the next steps needed to obtain a full picture of genotype-phenotype correlation and apply these findings to inform clinical practice. RECENT FINDINGS: So far, genome-wide association studies have defined at least 19 genomic regions that contain common DNA single nucleotide polymorphisms associated with LDL cholesterol, HDL cholesterol and/or triglycerides. Of these, eight represent novel loci in humans, whereas 11 genes have been previously implicated in lipoprotein metabolism. Many of the same loci with common variants have already been shown to lead to monogenic lipid disorders in humans and/or mice, suggesting that a spectrum of common and rare alleles at each validated locus contributes to blood lipid concentrations. SUMMARY: At least 19 loci harbor common variations that contribute to blood lipid concentrations in humans. Larger scale genome-wide association studies should identify additional loci, and sequencing of these loci should pinpoint all relevant alleles. With a full catalog of DNA polymorphisms in hand, a panel of lipid-related variants can be studied to provide clinical risk stratification and targeting of therapeutic interventions. 相似文献
154.
Cell cultures as models of cardiac mechanoelectric feedback 总被引:2,自引:2,他引:0
Zhang Y Sekar RB McCulloch AD Tung L 《Progress in biophysics and molecular biology》2008,97(2-3):367-382
Although stretch-activated currents have been extensively studied in isolated cells and intact heart in the context of mechanoelectric feedback (MEF) in the heart, quantitative data regarding other mechanical parameters such as pressure, shear, bending, etc, are still lacking at the multicellular level. Cultured cardiac cell monolayers have been used increasingly in the past decade as an in vitro model for the studies of fundamental mechanisms that underlie normal and pathological electrophysiology at the tissue level. Optical mapping makes possible multisite recording and analysis of action potentials and wavefront propagation, suitable for monitoring the electrophysiological activity of the cardiac cell monolayer under a wide variety of controlled mechanical conditions. In this paper, we review methodologies that have been developed or could be used to mechanically perturb cell monolayers, and present some new results on the acute effects of pressure, shear stress and anisotropic strain on cultured neonatal rat ventricular myocyte (NRVM) monolayers. 相似文献
155.
Isolation and characterization of a novel Bacillus strain from coffee phyllosphere showing antifungal activity 总被引:1,自引:0,他引:1
AIMS: The isolation and characterization of a novel coffee-associated Bacillus mojavensis strain, designated as strain AB1, and its survival on the coffee phyllosphere. METHODS AND RESULTS: A pair of 16S rDNA primers was designed to amplify a highly variable region within the 16S rDNA gene of Bacillus spp., with the purpose of identifying the AB1 isolate through PCR and sequence analysis. By this method, AB1 was identified as a strain of B. mojavensis. Bioassays were carried out to characterize the broad spectrum antifungal activity of AB1. Plant colonization studies revealed that AB1 could colonize the coffee phyllosphere better than Bacillus thuringiensis. CONCLUSIONS: These studies suggest that AB1 could be a new strain of B. mojavensis. AB1 is also shown to have antifungal activity against a wide spectrum of pathogenic fungi. The antifungal metabolite of AB1 has been partially characterized as a thermostable, protease- and alkali-resistant substance that is secreted into the surrounding medium. SIGNIFICANCE AND IMPACT OF THE STUDY: As far as is known, this is the first strain of B. mojavensis which has been identified as inhabiting the coffee phyllosphere. The study highlights the potential use of AB1 as an antifungal agent in the coffee crop and as a delivery agent of the insecticidal toxin of B. thuringiensis to the coffee phyllosphere. The 16S rRNA identification strategy discussed could also be used in the identification of other new Bacillus strains. 相似文献
156.
Yu BZ Poi MJ Ramagopal UA Jain R Ramakumar S Berg OG Tsai MD Sekar K Jain MK 《Biochemistry》2000,39(40):12312-12323
Pancreatic phospholipase A(2) (PLA2) shows a strong preference for the binding to the anionic interface and a consequent allosteric activation. In this paper, we show that virtually all the preference is mediated through 3 (Lys-53, -56, and -120) of the 12 cationic residues of bovine pancreatic PLA2. The lysine-to-methionine substitution enhances the binding of the enzyme to the zwitterionic interface, and for the K53,56,120M triple mutant at the zwitterionic interface is comparable to that for the wild type (WT) at the anionic interface. In the isomorphous crystal structure, the backbone folding of K53,56M K120,121A and WT are virtually identical, yet a significant change in the side chains of certain residues, away from the site of substitution, mostly at the putative contact site with the interface (i-face), is discernible. Such reciprocity, also supported by the spectroscopic results for the free and bound forms of the enzyme, is expected because a distal structural change that perturbs the interfacial binding could also affect the i-face. The results show that lysine-to-methionine substitution induces a structural change that promotes the binding of PLA2 to the interface as well as the substrate binding to the enzyme at the interface. The kinetic results are consistent with a model in which the interfacial Michaelis complex exists in two forms, and the complex that undergoes the chemical step is formed by the charge compensation of Lys-53 and -56. Analysis of the incremental changes in the kinetic parameters shows that the charge compensation of Lys-53 and -56 contributes to the activation and that of Lys-120 contributes only to the structural change that promotes the stability of the Michaelis complex at the interface. The charge compensation effects on these three residues also account for the differences in the anionic interface preference of the evolutionarily divergent secreted PLA2. 相似文献
157.
Roy S Saraswathi R Gupta S Sekar K Chatterji D Vijayan M 《Journal of molecular biology》2007,370(4):752-767
Mycobacterium smegmatis Dps degrades spontaneously into a species in which 16 C-terminal residues are cleaved away. A second species, in which all 26 residues constituting the tail were deleted, was cloned, expressed and purified. The first did not bind DNA but formed dodecamers like the native protein, while the second did not bind to DNA and failed to assemble into dodecamers, indicating a role in assembly also for the tail. In the crystal structure of the species without the entire C-terminal tail the molecule has an unusual open decameric structure resulting from the removal of two adjacent subunits from the original dodecameric structure of the native form. A Dps dodecamer could assemble with a dimer or one of two trimers (trimer-A and trimer-B) as intermediate. Trimer-A is the intermediate species in the M. smegmatis protein. Estimation of the surface area buried on trimerization indicates that association within trimer-B is weak. It weakens further when the C-terminal tail is removed, leading to the disruption of the dodecameric structure. Thus, the C-terminal tail has a dual role, one in DNA binding and the other in the assembly of the dodecamer. M. smegmatis Dps also has a short N-terminal tail. A species with nine N-terminal residues deleted formed trimers but not dodecamers in solution, unlike wild-type M. smegmatis Dps, under the same conditions. Unlike in solution, the N-terminal mutant forms dodecamers in the crystal. In native Dps, the N-terminal stretch of one subunit and the C-terminal stretch of a neighboring subunit lock each other into ordered positions. The deletion of one stretch results in the disorder of the other. This disorder appears to result in the formation of a trimeric species of the N-terminal deletion mutant contrary to the indication provided by the native structure. The ferroxidation site is intact in the mutants. 相似文献
158.
Rathinasabapathi Prabhakaran Ramasamy Karvembu Karuppannan Natarajan 《Inorganica chimica acta》2007,360(2):691-694
An unusual coordination mode of salicylaldehyde-N-phenylthiosemicarbazone (H2-Sal-Ptsc) ligand was observed in unusual ruthenium(III) carbonyl complex for the first time when it was reacted with [RuHCl(CO)(PPh3)3]. The EPR and electrochemical analysis conformed the formation of Ru(III) species. 相似文献
159.
Epigallocatechin‐3‐gallate suppresses the lipid deposition through the apoptosis during differentiation in bovine bone marrow mesenchymal stem cells
下载免费PDF全文
![点击此处可从《Cell biology international》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jin Young Jeong Sekar Suresh Mi Jang Mi Na Park Kuppannan Gobianand Seungkwon You Sung‐Heom Yeon Hyun‐Jeong Lee 《Cell biology international》2015,39(1):52-64
Epigallocatechin gallate (EGCG), a major component of tea, has known effects on obesity, fatty liver, and obesity‐related cancer. We explored the effects of EGCG on the differentiation of bovine mesenchymal stem cells (BMSCs, which are multipotent) in a dose‐ and time‐dependent manner. Differentiating BMSCs were exposed to various concentrations of EGCG (0, 10, 50, 100, and 200 µM) for 2, 4, and 6 days. BMSCs were cultured in Dulbecco's modified Eagle's medium (DMEM)/high‐glucose medium with adipogenic inducers for 6 days, and the expression levels of various genes involved in adipogenesis were measured using real‐time polymerase chain reaction (PCR) and Western blotting. We assessed apoptosis by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) staining of control and EGCG‐exposed cells. We found that EGCG significantly suppressed fat deposition and cell viability (P < 0.05). The mRNA and protein levels of various adipogenic factors were measured. Expression of the genes encoding peroxisome proliferator‐activated receptor gamma (PPARG), CCAAT/enhancer‐binding protein alpha (CEBPA), fatty acid‐binding protein 4 (FABP4), and stearoyl‐CoA desaturase (SCD) were diminished by EGCG during adipogenic differentiation (P < 0.05). We also found that EGCG lowered the expression levels of the adipogenic proteins encoded by these genes (P < 0.05). EGCG induced apoptosis during adipogenic differentiation (P < 0.05). Thus, exposure to EGCG potentially inhibits adipogenesis by triggering apoptosis; the data suggest that EGCG inhibits adipogenic differentiation in BMSCs. 相似文献
160.