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71.
We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions. 相似文献
72.
73.
Bjorn Kloosterman AM Anithakumari Pierre-Yves Chibon Marian Oortwijn Gerard C van der Linden Richard GF Visser Christian WB Bachem 《BMC plant biology》2012,12(1):17
Background
With the completion of genome sequences belonging to some of the major crop plants, new challenges arise to utilize this data for crop improvement and increased food security. The field of genetical genomics has the potential to identify genes displaying heritable differential expression associated to important phenotypic traits. Here we describe the identification of expression QTLs (eQTLs) in two different potato tissues of a segregating potato population and query the potato genome sequence to differentiate between cis- and trans-acting eQTLs in relation to gene subfunctionalization. 相似文献74.
75.
Rosalind A. Rosenthal Karl D. Huffman Leslie W. Fisette Christy A. Damphousse Wyeth B. Callaway Bernard Malfroy Susan R. Doctrow 《Journal of biological inorganic chemistry》2009,14(6):979-991
Superoxide dismutase/catalase mimetics, such as salen Mn complexes and certain metalloporphyrins, catalytically neutralize
reactive oxygen and nitrogen species, which have been implicated in the pathogenesis of many serious diseases. Both classes
of mimetic are protective in animal models of oxidative stress. However, only AEOL11207 and EUK-418, two uncharged Mn porphyrins,
have been shown to be orally bioavailable. In this study, EUK-418 and several new analogs (the EUK-400 series) were synthesized
and shown to exhibit superoxide dismutase, catalase, and peroxidase activities in vitro. Some also protected PC12 cells against
staurosporine-induced cell death. All EUK-400 compounds were stable in simulated gastric fluid, and most were substantially
more lipophilic than the salen Mn complexes EUK-189 and EUK-207, which lack oral activity. Pharmacokinetics studies demonstrate
the presence of all EUK-400 series compounds in the plasma of rats after oral administration. These EUK-400 series compounds
are potential oral therapeutic agents for cellular damage caused by oxidative stress.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
76.
H Sutton P Wyeth A P Allen O A Thurtle T K Hames M I Cawley D Ackery 《BMJ (Clinical research ed.)》1982,285(6349):1153-1154
Meta-iodobenzylguanidine, a guanethidine analogue, is a newly synthesised substance capable of imaging the adrenal medulla. In a woman in whom phaeochromocytoma has been diagnosed iodine-131-labelled metaiodobenzylguanidine was given intravenously; gamma-camera images showed bilateral adrenal tumours and uptake corresponding to bone and liver metastases. 131I-meta-iodobenzylguanidine is effective in localising phaeochromocytomas, and the technique is safe, specific, and non-invasive. 相似文献
77.
R P Wyeth B H Ackerman D L Vesely 《Biochemical and biophysical research communications》1990,173(3):1030-1037
The N-terminus consisting of amino acids (a.a.) 1-98 (i.e., proANF 1-98), C-terminus (i.e., ANF; a.a. 99-126) and midportion of N-terminus consisting of a.a. 31-67 (proANF 31-67; Vessel Dilator) of the 126 a.a. ANF prohormone were present in the urine in 5-to-8-fold increased concentrations versus their plasma concentrations in 6 dogs under basal conditions. With acute coronary occlusion the right atrial plasma concentrations of these peptides increased two-to-three-fold, while in the urine only proANF 31-67 increased (3.5-fold). Ventricular fibrillation caused a 4-to-10-fold increased secretion into the right atrial chamber with a simultaneous 3-to-4.7-fold increase in the urine of proANF 1-98, proANF 31-67, and ANF. This investigation demonstrates that proANF 1-98, proANF 31-67 and ANF are normally present in urine and increase in the urine with cardiac stimuli that cause their release from the heart. 相似文献
78.
79.
Background
A central problem in systems biology research is the identification and extension of biological modules–groups of genes or proteins participating in a common cellular process or physical complex. As a result, there is a persistent need for practical, principled methods to infer the modular organization of genes from genome-scale data.Results
We introduce a novel approach for the identification of modules based on the persistence of isolated gene groups within an evolving graph process. First, the underlying genomic data is summarized in the form of ranked gene–gene relationships, thereby accommodating studies that quantify the relevant biological relationship directly or indirectly. Then, the observed gene–gene relationship ranks are viewed as the outcome of a random graph process and candidate modules are given by the identifiable subgraphs that arise during this process. An isolation index is computed for each module, which quantifies the statistical significance of its survival time.Conclusions
The Miso (module isolation) method predicts gene modules from genomic data and the associated isolation index provides a module-specific measure of confidence. Improving on existing alternative, such as graph clustering and the global pruning of dendrograms, this index offers two intuitively appealing features: (1) the score is module-specific; and (2) different choices of threshold correlate logically with the resulting performance, i.e. a stringent cutoff yields high quality predictions, but low sensitivity. Through the analysis of yeast phenotype data, the Miso method is shown to outperform existing alternatives, in terms of the specificity and sensitivity of its predictions. 相似文献80.
Bair W 《Current opinion in neurobiology》2005,15(4):459-464
Increasingly systematic approaches to quantifying receptive fields in primary visual cortex, combined with inspired ideas about functional circuitry, non-linearities, and visual stimuli, are bringing new interest to classical problems. This includes the distinction and hierarchy between simple and complex cells, the mechanisms underlying the receptive field surround, and debates about optimal stimuli for mapping receptive fields. An important new problem arises from recent observations of stimulus-dependent spatial and temporal summation in primary visual cortex. It appears that the receptive field can no longer be considered unique, and we might have to relinquish this cherished notion as the embodiment of neuronal function in primary visual cortex. 相似文献