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11.
Nitric oxide (NO) is a janus faced chemical messenger, which, in the recent years, has been the focus of neurobiologists for its involvement in neurodegenerative disorders in particular, Parkinson's disease (PD). Nitric oxide synthase, the key enzyme involved in NO production exists in three known isoforms. The neuronal and inducible isoforms have been implicated in the pathogenesis of PD. These enzymes are subject to complex expressional and functional regulation involving mRNA diversity, phosphorylation and protein interaction. In the recent years, mRNA diversity and polymorphisms have been identified in the NOS isoforms. Some of these genetic variations have been associated with PD, indicating an etiological role for the NOS genes. This review mainly focuses on the NOS genes - their differential regulation and genetic heterogeneity, highlighting their significance in the pathobiology of PD. 相似文献
12.
GK Madhavilatha BV Joseph LK Paul RA Kumar R Hariharan S Mundayoor 《Journal of bacteriology》2012,194(16):4430
We report the annotated genome sequence of two clinical isolates of Mycobacterium tuberculosis isolated from Kerala, India. 相似文献
13.
Cellular quiescence is characterized not only by reduced mitotic and metabolic activity but also by altered gene expression. Growing evidence suggests that quiescence is not merely a basal state but is regulated by active mechanisms. To understand the molecular programme that governs reversible cell cycle exit, we focused on quiescence-related gene expression in a culture model of myogenic cell arrest and activation. Here we report the identification of quiescence-induced genes using a gene-trap strategy. Using a retroviral vector, we generated a library of gene traps in C2C12 myoblasts that were screened for arrest-induced insertions by live cell sorting (FACS-gal). Several independent gene- trap lines revealed arrest-dependent induction of betagal activity, confirming the efficacy of the FACS screen.The locus of integration was identified in 15 lines. In three lines,insertion occurred in genes previously implicated in the control of quiescence, i.e. EMSY - a BRCA2--interacting protein, p8/com1 - a p300HAT -- binding protein and MLL5 - a SET domain protein. Our results demonstrate that expression of chromatin modulatory genes is induced in G0, providing support to the notion that this reversibly arrested state is actively regulated. 相似文献
14.
Racial disparity in spontaneous preterm birth (PTB) between African Americans and Caucasians in the US is unexplained, but
is probably related to differences in amniotic fluid (AF) inflammatory cytokine profiles. Therefore, this study analyzed the
association of 34 single nucleotide polymorphisms (SNPs) in TNF-α and its receptor genes (TNFR1 and TNFR2) with AF TNF-α and soluble TNF receptor (R1 and R2) concentrations in PTB. Samples consisted of African American and Caucasian
cases (PTB), and controls (term birth) for which both cytokine, and maternal and fetal genotype data were available. Analyses
were performed with genotype, case, and maker-status interaction in the model for log transformed cytokine concentrations.
In Caucasians, two interactions between genotype and pregnancy outcome associated with cytokine concentrations, whereas 14
gene variants in African Americans showed interactions with pregnancy outcome, and 13 showed association with genetic markers.
In conclusion, cytokine concentrations in African American preterm births can be partially explained by interactions between
pregnancy outcome, SNPs and infection. This does not appear to be the case in Caucasians. These findings may be important
in understanding disparity in rates of PTB between the two populations.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
15.
Srinivasagan Ramkumar Xingjun Fan Benlian Wang Sichun Yang Vincent M. Monnier 《生物化学与生物物理学报:疾病的分子基础》2018,1864(11):3595-3604
Cysteine (Cys) residues are major causes of crystallin disulfide formation and aggregation in aging and cataractous human lenses. We recently found that disulfide linkages are highly and partly conserved in β- and γ-crystallins, respectively, in human age-related nuclear cataract and glutathione depleted LEGSKO mouse lenses, and could be mimicked by in vitro oxidation. Here we determined which Cys residues are involved in disulfide-mediated crosslinking of recombinant human γD-crystallin (hγD). In vitro diamide oxidation revealed dimer formation by SDS-PAGE and LC-MS analysis with Cys 111-111 and C111-C19 as intermolecular disulfides and Cys 111-109 as intramolecular sites. Mutation of Cys111 to alanine completely abolished dimerization. Addition of αB-crystallin was unable to protect Cys 111 from dimerization. However, Cu2+-induced hγD-crystallin aggregation was suppressed up to 50% and 80% by mutants C109A and C111A, respectively, as well as by total glutathionylation. In contrast to our recently published results using ICAT-labeling method, manual mining of the same database confirmed the specific involvement of Cys111 in disulfides with no free Cys111 detectable in γD-crystallin from old and cataractous human lenses. Surface accessibility studies show that Cys111 in hγD is the most exposed Cys residue (29%), explaining thereby its high propensity toward oxidation and polymerization in the aging lens. 相似文献
16.
Alan Xiangdong Wang Jie Chen Qian Zhao Li-Qiang Sun Jacques Friborg Fei Yu Dennis Hernandez Andrew C. Good Herbert E. Klei Ramkumar Rajamani Kathy Mosure Jay O. Knipe Danshi Li Jialong Zhu Paul C. Levesque Fiona McPhee Nicholas A. Meanwell Paul M. Scola 《Bioorganic & medicinal chemistry letters》2017,27(3):590-596
The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relating to structure-activity relationships as well as the pharmacokinetic and cardiovascular profiles of these analogues is provided. 相似文献
17.
Rishiram Ramanan Krishnamurthi Kannan Nadimuthu Vinayagamoorthy Kunga Mohan Ramkumar Saravana Devi Sivanesan Tapan Chakrabarti 《Biotechnology and Bioprocess Engineering》2009,14(1):32-37
Carbonic anhydrase enzyme, one of the fastest known enzymes, remains largely unexplored in prokaryotes when compared to its
mammalian counterparts despite its ubiquity. In this study, the enzyme has been purified from Bacillus subtilis SA3 using sequential Sephadex G-75 chromatography, DEAE cellulose chromatography, and sepharose-4B-L-tyrosinesulphanilamide
affinity chromatography and characterized to provide additional insights into its properties. The apparent molecular mass
of carbonic anhydrase obtained by SDS-PAGE was found to be approximately 37 kDa. Isoelectric focusing of the purified enzyme
revealed an isoelectric point (pI) of around 6.1 when compared with marker. The presence of metal ions such as Zn2+, Co2+, Cu2+, Fe3+, Mg2+, and anion SO4− increased enzyme activity while strong inhibition was observed in the presence of Hg2+, Cl−, HCO3−, and metal chelator EDTA. The optimum pH and temperature for the enzyme were found to be 8.3 and 37°C, respectively. Enzyme
kinetics with p-nitrophenyl acetate as substrate at pH 8.3 and 37°C determined the Vmax and Km values of the enzyme to be 714.28 μmol/mg protein/min and 9.09 mM, respectively. The Ki value for acetazolamide was 0.22 mM, compared to 0.099 mM for sulphanilamide. The results from N-terminal amino acid sequencing
imply the purified protein is a putative beta-carbonic anhydrase with close similarities to CAs from plants, microorganisms. 相似文献
18.
G. Ramkumar A. K. P. Sivaranjani Manish K. Pandey K. Sakthivel N. Shobha Rani I. Sudarshan G. S. V. Prasad C. N. Neeraja R. M. Sundaram B. C. Viraktamath M. S. Madhav 《Molecular breeding : new strategies in plant improvement》2010,26(4):735-740
Kernel length in rice (Oryza sativa L.) is controlled by various quantitative trait loci of which GS3 is the most important, being responsible for 80–90% of the variation in kernel length. A mutation in the second exon of this gene has been reported to be associated with maximum variations in the kernel length. We have developed a simple PCR-based marker system named DRR-GL which targets the functional nucleotide polymorphism at GS3. This marker system has the advantages that it is easy to use, saves time and cost, and is amenable for large-scale marker-assisted selection for the trait of kernel length. Validation of this marker in a segregating population and 152 rice varieties, which includes 30 elite basmati varieties, reveals its effective co-segregation and association with the traits of kernel length as well as kernel elongation after cooking. We recommend utilization of this simple, low-cost marker system in breeding programs targeted at improvement of key rice grain quality traits, kernel length and kernel elongation. 相似文献
19.
20.
Zoran J. N. Steinmann Mara Hauck Ramkumar Karuppiah Ian J. Laurenzi Mark A. J. Huijbregts 《The International Journal of Life Cycle Assessment》2014,19(5):1146-1155