全文获取类型
收费全文 | 65篇 |
免费 | 4篇 |
专业分类
69篇 |
出版年
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 2篇 |
2013年 | 2篇 |
2012年 | 1篇 |
2011年 | 3篇 |
2009年 | 3篇 |
2006年 | 1篇 |
2005年 | 4篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1971年 | 2篇 |
1934年 | 1篇 |
排序方式: 共有69条查询结果,搜索用时 0 毫秒
11.
12.
Elena Turola Salvatore Petta Ester Vanni Fabiola Milosa Luca Valenti Rosina Critelli Luca Miele Livia Maccio Vincenza Calvaruso Anna L. Fracanzani Marcello Bianchini Nazarena Raos Elisabetta Bugianesi Serena Mercorella Marisa Di Giovanni Antonio Craxì Silvia Fargion Antonio Grieco Calogero Cammà Franco Cotelli Erica Villa 《Disease models & mechanisms》2015,8(9):1037-1046
13.
Simeone JP Bugianesi RL Ponpipom MM Yang YT Lo JL Yudkovitz JB Cui J Mount GR Ren RN Creighton M Mao AH Vincent SH Cheng K Goulet MT 《Bioorganic & medicinal chemistry letters》2002,12(22):3329-3332
The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs. 相似文献
14.
Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications 总被引:12,自引:1,他引:11
Ribosomal RNAs have secondary structures that are maintained by internal
Watson-Crick pairing. Through analysis of chordate, arthropod, and plant 5S
ribosomal RNA sequences, we show that Darwinian selection operates on these
nucleotide sequences to maintain functionally important secondary
structure. Insect phylogenies based on nucleotide positions involved in
pairing and the production of secondary structure are incongruent with
those constructed on the basis of positions that are not. Furthermore,
phylogeny reconstruction using these nonpairing bases is concordant with
other, morphological data.
相似文献
15.
Bao J Miao S Kayser F Kotliar AJ Baker RK Doss GA Felix JP Bugianesi RM Slaughter RS Kaczorowski GJ Garcia ML Ha SN Castonguay L Koo GC Shah K Springer MS Staruch MJ Parsons WH Rupprecht KM 《Bioorganic & medicinal chemistry letters》2005,15(2):447-451
Kv1.3, the voltage-gated potassium channel in human T cells, represents a new target for treating immunosuppression and autoimmune diseases. Correolide (1), a pentacyclic natural product, is a potent and selective Kv1.3 channel blocker. Simplification of correolide via removal of its E-ring generates enone 4, whose modification produced a new series of tetracyclic Kv1.3 blockers. The structure-activity relationship for this class of compounds in two functional assays, Rb_Kv and human T cell proliferation, is presented herein. The most potent analog 43 is 15-fold more potent than correolide as inhibitor of human T cell proliferation. 相似文献
16.
17.
18.
Bradley RD; Adkins RM; Honeycutt RL; McDonald JH 《Molecular biology and evolution》1998,15(6):709-717
Using the strictly neutral model as a null hypothesis, we tested for
deviations from expected levels of nucleotide polymorphism at the alcohol
dehydrogenase locus (Adh-1) within and among four species of pocket gophers
(Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G.
attwateri). The complete protein-encoding region was examined, and 10
unique alleles, representing both electromorphic and cryptic alleles, were
used to test hypotheses (e.g., the neutral model) concerning the
maintenance of genetic variation. Nineteen variable sites were identified
among the 10 alleles examined, including 9 segregating sites occurring in
synonymous positions and 10 that were nonsynonymous. Several statistical
methods, including those that test for within-species variation as well as
those that examine variation within and among species, failed to reject the
null hypothesis that variation (both within and between species of Geomys)
at the Adh locus is consistent with the neutral theory. However, there was
significant heterogeneity in the ratio of polymorphism to divergence across
the gene, with polymorphisms clustered in the first half of the coding
region and fixed differences clustered in the second half of the gene. Two
alternative hypotheses are discussed as possible explanations for this
heterogeneity: an old balanced polymorphism in the first half of the gene
or a recent selective sweep in the second half of the gene.
相似文献
19.
20.
Middleton RE Sanchez M Linde AR Bugianesi RM Dai G Felix JP Koprak SL Staruch MJ Bruguera M Cox R Ghosh A Hwang J Jones S Kohler M Slaughter RS McManus OB Kaczorowski GJ Garcia ML 《Biochemistry》2003,42(46):13698-13707
ShK, a peptide isolated from Stichodactyla helianthus venom, blocks the voltage-gated potassium channels, K(v)1.1 and K(v)1.3, with similar high affinity. ShK-Dap(22), a synthetic derivative in which a diaminopropionic acid residue has been substituted at position Lys(22), has been reported to be a selective K(v)1.3 inhibitor and to block this channel with equivalent potency as ShK [Kalman et al. (1998) J. Biol. Chem. 273, 32697-32707]. In this study, a large body of evidence is presented which indicates that the potencies of wild-type ShK peptide for both K(v)1.3 and K(v)1.1 channels have been previously underestimated. Therefore, the affinity of ShK-Dap(22) for both channels appears to be ca. 10(2)-10(4)-fold weaker than ShK. ShK-Dap(22) does display ca. 20-fold selectivity for human K(v)1.3 vs K(v)1.1 when measured by the whole-cell voltage clamp method but not in equilibrium binding assays. ShK-Dap(22) has low affinity for K(v)1.2 channels, but heteromultimeric K(v)1.1-K(v)1.2 channels form a receptor with ca. 200-fold higher affinity for ShK-Dap(22) than K(v)1.1 homomultimers. In fact, K(v)1.1-K(v)1.2 channels bind ShK-Dap(22) with only ca. 10-fold less potency than ShK and reveal a novel pharmacology not predicted from the homomultimers of K(v)1.1 or K(v)1.2. The concentrations of ShK-Dap(22) needed to inhibit human T cell activation were ca. 10(3)-fold higher than those of ShK, in good correlation with the relative affinities of these peptides for inhibiting K(v)1.3 channels. All of these data, taken together, suggest that ShK-Dap(22) will not have the same in vivo immunosuppressant efficacy of other K(v)1.3 blockers, such as margatoxin or ShK. Moreover, ShK-Dap(22) may have undesired side effects due to its interaction with heteromultimeric K(v)1.1-K(v)1.2 channels, such as those present in brain and/or peripheral tissues. 相似文献