全文获取类型
收费全文 | 62篇 |
免费 | 11篇 |
出版年
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 3篇 |
2011年 | 2篇 |
2009年 | 5篇 |
2008年 | 2篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1981年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1975年 | 2篇 |
排序方式: 共有73条查询结果,搜索用时 378 毫秒
61.
Yoshihara HA Apriletti JW Baxter JD Scanlan TS 《Bioorganic & medicinal chemistry letters》2001,11(21):2821-2825
We synthesized an analogue of the thyromimetic GC-1 bearing the same hydrophobic appendage as the estrogen receptor antagonist ICI-164,384. While having reduced affinity for the thyroid hormone receptors compared to GC-1, it behaves in a manner consistent with a competitive antagonist in a transactivation assay. 相似文献
62.
Chun-Chi Liu Chin-Chung Lin Ker-Chau Li Wen-Shyen E Chen Jiun-Ching Chen Ming-Te Yang Pan-Chyr Yang Pei-Chun Chang Jeremy JW Chen 《BMC bioinformatics》2007,8(1):164
Background
Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos. 相似文献63.
64.
Basolateral K channels in an insect epithelium. Channel density, conductance, and block by barium 下载免费PDF全文
K channels in the basolateral membrane of insect hindgut were studied using current fluctuation analysis and microelectrodes. Locust recta were mounted in Ussing-type chambers containing Cl-free saline and cyclic AMP (cAMP). A transepithelial K current was induced by raising serosal [K] under short-circuit conditions. Adding Ba to the mucosal (luminal) side under these conditions had no effect; however, serosal Ba reversibly inhibited the short-circuit current (Isc), increased transepithelial resistance (Rt), and added a Lorentzian component to power density spectra of the Isc. A nonlinear relationship between corner frequency and serosal [Ba] was observed, which suggests that the rate constant for Ba association with basolateral channels increased as [Ba] was elevated. Microelectrode experiments revealed that the basolateral membrane hyperpolarized when Ba was added: this change in membrane potential could explain the nonlinearity of the 2 pi fc vs. [Ba] relationship if external Ba sensed about three-quarters of the basolateral membrane field. Conventional microelectrodes were used to determine the correspondence between transepithelially measured current noise and basolateral membrane conductance fluctuations, and ion-sensitive microelectrodes were used to measure intracellular K activity (acK). From the relationship between the net electrochemical potential for K across the basolateral membrane and the single channel current calculated from noise analysis, we estimate that the conductance of basolateral K channels is approximately 60 pS, and that there are approximately 180 million channels per square centimeter of tissue area. 相似文献
65.
Large scale purification of the nuclear thyroid hormone receptor from rat liver and sequence-specific binding of the receptor to DNA 总被引:2,自引:0,他引:2
Methodology is reported for extracting thyroid hormone receptors from rat liver nuclei and for purifying these such that certain receptor properties can be examined. The extraction technique resulted in 1700 pmol of receptor/2 kg of liver and bypasses centrifugation in dense sucrose. The receptor was then purified by sequential heparin-Sepharose, DEAE-Sepharose, and phospho-Ultrogel chromatography and size exclusion and hydrophobic interaction high performance liquid chromatography. These steps yielded 23-35 micrograms of receptor at 0.7-1.5% purity from two 2-kg liver preparations. The cross-linkers disuccinimidyl suberate and N-succinimidyl-6-(4-azido-2-nitrophenylamino)hexanoate were employed to covalently attach 125I-labeled 3,5,3'-triiodo-L-thyronine (T3) to the purified receptor. Autoradiography after denaturing polyacrylamide gel electrophoresis revealed major 49,000 Mr and minor 58,000 Mr specific T3-binding proteins. The purified receptors exhibited high affinity (Kd = 100 pM) single site T3-binding activity. Because of the high affinity and specificity of [125I]T3 for the receptor, it was possible to uniquely identify the receptor containing DNA-protein complexes in a gel retardation assay and thus directly demonstrate for the first time that the receptor can specifically recognize sequences in the 5'-flanking DNA of the rat growth hormone gene. [125I]T3-labeled receptor migrated at the same position as the major gel-retarded 32P-labeled DNA band. Specific DNA competed for the binding much more strongly than nonspecific DNA. Thus, the purification procedure results in relatively large quantities of receptor at a purity sufficient for detecting and studying a number of its properties including specific DNA binding activity. 相似文献
66.
67.
Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster 总被引:9,自引:0,他引:9
It has been proposed that the degree of recombination for a genomic region
will affect the level of both nucleotide heterozygosity and the density of
transposable elements. Both features of genomic diversity have been
examined in a number of recent reports for regions undergoing relatively
normal levels of recombination in Drosophila melanogaster. In this study
the genomic variation associated with yellow-achaete- scute loci located at
the tip of the X chromosome is examined by six- cutter restriction mapping.
In this region, as usual for regions adjacent to telomeres, crossing-over
is dramatically reduced, and published studies of visible mutants indicate
extremely little restriction-map variation. Eight six-cutter restriction
endonucleases were used to locate sequence variation in 14- and 16.5-kb
regions in 109 lines sampled from North America, Africa, and Europe. The
overall level of heterozygosity is estimated as 0.29%. Nine large
insertions, all presumed to be transposable elements, were observed.
Base-pair heterozygosity appears to be reduced compared with regions having
normal levels of recombination. The estimated heterozygosity is much higher
than reported in earlier studies of restriction-map variation among visible
mutations in the complex. The incidence of large insertions is not elevated
compared with that in other regions of the genome. This suggests that
asymmetric synapsis and exchange is not an important mechanism for the
elimination of transposable elements.
相似文献
68.
Selective modulation of thyroid hormone receptor action 总被引:3,自引:0,他引:3
Baxter JD Dillmann WH West BL Huber R Furlow JD Fletterick RJ Webb P Apriletti JW Scanlan TS 《The Journal of steroid biochemistry and molecular biology》2001,76(1-5):31-42
Thyroid hormones have some actions that might be useful therapeutically, but others that are deleterious. Potential therapeutically useful actions include those to induce weight loss and lower plasma cholesterol levels. Potential deleterious actions are those on the heart to induce tachycardia and arrhythmia, on bone to decrease mineral density, and on muscle to induce wasting. There have been successes in selectively modulating the actions of other classes of hormones through various means, including the use of pharmaceuticals that have enhanced affinities for certain receptor isoforms. Thus, there is reason to pursue selective modulation of thyroid hormone receptor (TR) function, and several agents have been shown to have some β-selective, hepatic selective and/or cardiac sparring activities, although development of these was largely not based on detailed understanding of mechanisms for the specificity. The possibility of selectively targeting the TRβ was suggested by the findings that there are - and β-TR forms and that the TR-forms may preferentially regulate the heart rate, whereas many other actions of these hormones are mediated by the TRβ. We determined X-ray crystal structures of the TR and TRβ ligand-binding domains (LBDs) complexed with the thyroid hormone analog 3,5,3′-triiodithyroacetic acid (Triac). The data suggested that a single amino acid difference in the ligand-binding cavities of the two receptors could affect hydrogen bonding in the receptor region, where the ligand's 1-position substituent fits and might be exploited to generate β-selective ligands. The compound GC-1, with oxoacetate in the 1-position instead of acetate as in Triac, exhibited TRβ-selective binding and actions in cultured cells. An X-ray crystal structure of the GC-1-TRβ LBD complex suggests that the oxoacetate does participate in a network of hydrogen bonding in the TR LBD polar pocket. GC-1 displayed actions in tadpoles that were TRβ-selective. When administered to mice, GC-1 was as effective in lowering plasma cholesterol levels as T3, and was more effective than T3 in lowering plasma triglyceride levels. At these doses, GC-1 did not increase the heart rate. GC-1 was also less active than T3 in modulating activities of several other cardiac parameters, and especially a cardiac pacemaker channel such as HCN-2, which may participate in regulation of the heart rate. GC-1 showed intermediate activity in suppressing plasma thyroid stimulating hormone (TSH) levels. The tissue/plasma ratio for GC-1 in heart was also less than for the liver. These data suggest that compounds can be generated that are TR-selective and that compounds with this property and/or that exhibit selective uptake, might have clinical utility as selective TR modulators. 相似文献
69.
A total of 27Fusarium culmorum isolates from Germany and 41F. graminearum isolates from Kenya were investigated for aggressiveness and mycotoxin production on wheat ears. In addition, ergosterol content of the kernels from ears inoculated withF. graminearum was determined and theF. culmorum isolates were tested for mycotoxin productionin vitro. For both pathogens, isolates markedly differed in aggressiveness. 59% and 37% of theF. culmorum isolates produced NIV and DON, respectively,in vivo andin vitro. The DON-producing isolates also produced 3-acDONin vitro. The more aggressive isolates produced mainly DON while the less aggressive isolates produced mainly NIV. 12% and 85% of theF. graminearum isolates produced NIV and DON, respectively. The highly aggressive isolates produced higher amounts of DON, aggressiveness being highly correlated to DON content in the kernels. NIV-producing isolates were less aggressive. Ergosterol content of kernels was moderately correlated to aggressiveness but highly correlated to DON content. Disease severity was associated with kernel weight reduction. 相似文献
70.