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排序方式: 共有145条查询结果,搜索用时 15 毫秒
21.
Helen Louise May-Simera Qin Wan Balendu Shekhar Jha Juliet Hartford Vladimir Khristov Roba Dejene Justin Chang Sarita Patnaik Quanlong Lu Poulomi Banerjee Jason Silver Christine Insinna-Kettenhofen Dishita Patel Mostafa Lotfi May Malicdan Nathan Hotaling Arvydas Maminishkis Rupa Sridharan Kapil Bharti 《Cell reports》2018,22(1):189-205
22.
Sehrawat B Sridharan M Ghosh S Robson P Cass CE Mackey JR Greiner R Damaraju S 《Human genetics》2011,130(4):529-537
Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However,
the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify
additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed
a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single
nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus
association tests to determine statistical significance for the observed differences in allele frequencies between cases and
controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153
cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from
four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls
in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs
identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage
III from Alberta population or independent validation in Caucasian cohorts elsewhere. 相似文献
23.
Nesterenko VV Zygmunt AC Rajamani S Belardinelli L Antzelevitch C 《American journal of physiology. Heart and circulatory physiology》2011,301(4):H1615-H1624
Block of Na(+) channel conductance by ranolazine displays marked atrial selectivity that is an order of magnitude higher that of other class I antiarrhythmic drugs. Here, we present a Markovian model of the Na(+) channel gating, which includes activation-inactivation coupling, aimed at elucidating the mechanisms underlying this potent atrial selectivity of ranolazine. The model incorporates experimentally observed differences between atrial and ventricular Na(+) channel gating, including a more negative position of the steady-state inactivation curve in atrial versus ventricular cells. The model assumes that ranolazine requires a hydrophilic access pathway to the channel binding site, which is modulated by both activation and inactivation gates of the channel. Kinetic rate constants were obtained using guarded receptor analysis of the use-dependent block of the fast Na(+) current (I(Na)). The model successfully reproduces all experimentally observed phenomena, including the shift of channel availability, the sensitivity of block to holding or diastolic potential, and the preferential block of slow versus fast I(Na.) Using atrial and ventricular action potential-shaped voltage pulses, the model confirms significantly greater use-dependent block of peak I(Na) in atrial versus ventricular cells. The model highlights the importance of action potential prolongation and of a steeper voltage dependence of the time constant of unbinding of ranolazine from the atrial Na(+) channel in the development of use-dependent I(Na) block. Our model predictions indicate that differences in channel gating properties as well as action potential morphology between atrial and ventricular cells contribute equally to the atrial selectivity of ranolazine. The model indicates that the steep voltage dependence of ranolazine interaction with the Na(+) channel at negative potentials underlies the mechanism of the predominant block of I(Na) in atrial cells by ranolazine. 相似文献
24.
AFP-Pred: A random forest approach for predicting antifreeze proteins from sequence-derived properties 总被引:1,自引:0,他引:1
Kandaswamy KK Chou KC Martinetz T Möller S Suganthan PN Sridharan S Pugalenthi G 《Journal of theoretical biology》2011,270(1):56-3077
Some creatures living in extremely low temperatures can produce some special materials called “antifreeze proteins” (AFPs), which can prevent the cell and body fluids from freezing. AFPs are present in vertebrates, invertebrates, plants, bacteria, fungi, etc. Although AFPs have a common function, they show a high degree of diversity in sequences and structures. Therefore, sequence similarity based search methods often fails to predict AFPs from sequence databases. In this work, we report a random forest approach “AFP-Pred” for the prediction of antifreeze proteins from protein sequence. AFP-Pred was trained on the dataset containing 300 AFPs and 300 non-AFPs and tested on the dataset containing 181 AFPs and 9193 non-AFPs. AFP-Pred achieved 81.33% accuracy from training and 83.38% from testing. The performance of AFP-Pred was compared with BLAST and HMM. High prediction accuracy and successful of prediction of hypothetical proteins suggests that AFP-Pred can be a useful approach to identify antifreeze proteins from sequence information, irrespective of their sequence similarity. 相似文献
25.
26.
Sven Ruf Mahanandeesha Siddappa Hallur Nisha K. Anchan Indu N. Swamy Karthikai Raj Murugesan Sayantani Sarkar Lokesh Kananti Narasimhulu V.P. Rama Kishore Putta Shama Shaik Devaraj Venkatapura Chandrasekar Vishal Subhash Mane Sanjay Venkatachalapathi Kadnur Juluri Suresh Ravi Kanth Bhamidipati Manvi Singh Raghunadha Reddy Burri Rajendra Kristam Herman Schreuder Sridharan Rajagopal 《Bioorganic & medicinal chemistry letters》2018,28(5):922-925
Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ~80% at 2?h when dosed in mice orally at 50?mg/kg. 相似文献
27.
28.
S. K. Grover K. Sridharan K. K. Srivastava 《International journal of biometeorology》1987,31(2):163-168
The sequential changes in serum total protein concentration and in various electrophoretic fractions among lowlanders during two years of stay at high altitude (4,000 m) were determined and compared with that of high altitude natives (Ladakhis). The albumin to globulin ratio decreased during the early period of exposure to altitude among lowlanders and continued to remain at that level with minor fluctuations during the entire period of stay at altitude. Among the high altitude natives, a decreased albumin to globulin ratio with low serum protein concentration was observed. The composition of globulins separated electro-phoretically was of similar pattern in altitude natives and in lowlanders after a stay of two years at altitude. Among these subjects the-globulin was significantly higher as compared to values at sea level. 相似文献
29.
30.
Sudharsan Sridharan Nigel Howard Micha? B?aszczyk Tom L. Blundell 《Journal of molecular biology》2010,397(1):290-7483
EntC, one of two isochorismate synthases in Escherichia coli, is specific to the biosynthesis of the siderophore enterobactin. Here, we report the crystal structure of EntC in complex with isochorismate and Mg2+at 2.3 Å resolution, the first structure of a chorismate-utilizing enzyme with a non-aromatic reaction product. EntC exhibits a complex α+β fold like the other chorismate-utilizing enzymes, such as salicylate synthase and anthranilate synthase. Comparison of active site structures allowed the identification of several residues, not discussed previously, that might be important for the isochorismate activity of the EntC. Although EntC, MenF and Irp9 all convert chorismate to isochorismate, only Irp9 subsequently exhibits isochorismate pyruvate lyase activity resulting in the formation of salicylate and pyruvate as the reaction products. With a view to understanding the roles of these amino acid residues in the conversion of chorismate to isochorismate and to obtaining clues about the pyruvate lyase activity of Irp9, several mutants of EntC were generated in which the selected residues in EntC were substituted for those of Irp9: these included A303T, L304A, F327Y, I346L and F359Q mutations. Biochemical analysis of these mutants indicated that the side chain of A303 in EntC may be crucial in the orientation of the carbonyl to allow formation of a hydrogen bond with isochorismate. Some mutations, such as L304A and F359Q, give rise to a loss of catalytic activity, whereas others, such as F327Y and I346L, show that subtle changes in the otherwise closely similar active sites influence activity. We did not find a combination of these residues that conferred pyruvate lyase activity. 相似文献