全文获取类型
收费全文 | 91篇 |
免费 | 4篇 |
出版年
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 3篇 |
2013年 | 1篇 |
2012年 | 4篇 |
2011年 | 1篇 |
2010年 | 1篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 10篇 |
2006年 | 6篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 11篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1986年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有95条查询结果,搜索用时 15 毫秒
1.
2.
Nielsen J; Peixoto AA; Piccin A; Costa R; Kyriacou CP; Chalmers D 《Molecular biology and evolution》1994,11(6):839-853
The region of the clock gene period (per) that encodes a repetitive tract
of threonine-glycine (Thr-Gly) pairs has been compared between Dipteran
species both within and outside the Drosophilidae. All the non-
Drosophilidae sequences in this region are short and present a remarkably
stable picture compared to the Drosophilidae, in which the region is much
larger and extremely variable, both in size and composition. The
accelerated evolution in the repetitive region of the Drosophilidae appears
to be mainly due to an expansion of two ancestral repeats, one encoding a
Thr-Gly dipeptide and the other a pentapeptide rich in serine, glycine, and
asparagine or threonine. In some drosophilids the expansion involves a
duplication of the pentapeptide sequence, but in Drosophila pseudoobscura
both the dipeptide and the pentapeptide repeats are present in larger
numbers. In the nondrosophilids, however, the pentapeptide sequence is
represented by one copy and the dipeptide by two copies. These observations
fulfill some of the predictions of recent theoretical models that have
simulated the evolution of repetitive sequences.
相似文献
3.
4.
5.
I Abbaszade R Q Liu F Yang S A Rosenfeld O H Ross J R Link D M Ellis M D Tortorella M A Pratta J M Hollis R Wynn J L Duke H J George M C Hillman K Murphy B H Wiswall R A Copeland C P Decicco R Bruckner H Nagase Y Itoh R C Newton R L Magolda J M Trzaskos T C Burn 《The Journal of biological chemistry》1999,274(33):23443-23450
Aggrecan is responsible for the mechanical properties of cartilage. One of the earliest changes observed in arthritis is the depletion of cartilage aggrecan due to increased proteolytic cleavage within the interglobular domain. Two major sites of cleavage have been identified in this region at Asn(341)-Phe(342) and Glu(373)-Ala(374). While several matrix metalloproteinases have been shown to cleave at Asn(341)-Phe(342), an as yet unidentified protein termed "aggrecanase" is responsible for cleavage at Glu(373)-Ala(374) and is hypothesized to play a pivotal role in cartilage damage. We have identified and cloned a novel disintegrin metalloproteinase with thrombospondin motifs that possesses aggrecanase activity, ADAMTS11 (aggrecanase-2), which has extensive homology to ADAMTS4 (aggrecanase-1) and the inflammation-associated gene ADAMTS1. ADAMTS11 possesses a number of conserved domains that have been shown to play a role in integrin binding, cell-cell interactions, and extracellular matrix binding. We have expressed recombinant human ADAMTS11 in insect cells and shown that it cleaves aggrecan at the Glu(373)-Ala(374) site, with the cleavage pattern and inhibitor profile being indistinguishable from that observed with native aggrecanase. A comparison of the structure and expression patterns of ADAMTS11, ADAMTS4, and ADAMTS1 is also described. Our findings will facilitate the study of the mechanisms of cartilage degradation and provide targets to search for effective inhibitors of cartilage depletion in arthritic disease. 相似文献
6.
Varnes JG Gardner DS Santella JB Duncia JV Estrella M Watson PS Clark CM Ko SS Welch P Covington M Stowell N Wadman E Davies P Solomon K Newton RC Trainor GL Decicco CP Wacker DA 《Bioorganic & medicinal chemistry letters》2004,14(7):1645-1649
The discovery of novel and selective small molecule antagonists of the CC Chemokine Receptor-3 (CCR3) is presented. Simple conversion from a 4- to 3-benzylpiperidine gave improved selectivity for CCR3 over the serotonin 5HT(2A) receptor. Chiral resolution and exploration of mono- and disubstitution of the N-propylurea resulted in several 3-benzylpiperidine N-propylureas with CCR3 binding IC(50)s under 5 nM. Data from in vitro calcium mobilization and chemotaxis assays for these compounds ranged from high picomolar to low nanomolar EC(50)s and correlated well with antagonist binding IC(50)s. 相似文献
7.
Wacker DA Santella JB Gardner DS Varnes JG Estrella M DeLucca GV Ko SS Tanabe K Watson PS Welch PK Covington M Stowell NC Wadman EA Davies P Solomon KA Newton RC Trainor GL Friedman SM Decicco CP Duncia JV 《Bioorganic & medicinal chemistry letters》2002,12(13):1785-1789
CCR3 antagonist leads with IC(50) values in the microM range were converted into low nM binding compounds that displayed in vitro inhibition of human eosinophil chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n-propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n-propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited single digit nanomolar IC(50) values for CCR3. 相似文献
8.
Xue CB He X Roderick J Corbett RL Duan JJ Liu RQ Covington MB Qian M Ribadeneira MD Vaddi K Christ DD Newton RC Trzaskos JM Magolda RL Wexler RR Decicco CP 《Bioorganic & medicinal chemistry letters》2003,13(24):4299-4304
Modifications of the lead TACE inhibitor 1 (N-hydroxy-trans-2-[[4-(4-quinolinyloxymethyl)anilinyl]carbonyl]-1-cyclohexanecarboxamide) at the cyclohexyl ring and the quinoline moiety led to the identification of a series of piperidine containing TACE inhibitors with potent activity in the inhibition of TNF-alpha release in the whole blood assay (WBA). The most potent analogue IM491 [N-hydroxy-(5S,6S)-1-methyl-6-[[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl]-5-piperidinecarboxamide] exhibited an IC(50) value of 20 nM in WBA with excellent selectivity over MMP-1, -2 and -9 and is orally bioavailable with an F value of 43% in beagle dogs. 相似文献
9.
Peptide-based alpha-ketoamides, alpha-ketoesters and alpha-diketones were designed, synthesized and evaluated against HCV NS3 protease. Alpha-ketoamides have the highest affinity among the three classes, with 8 being the most potent inhibitor with an IC50 of 340 nM. 相似文献
10.
Carter PH Brown GD Friedrich SR Cherney RJ Tebben AJ Lo YC Yang G Jezak H Solomon KA Scherle PA Decicco CP 《Bioorganic & medicinal chemistry letters》2007,17(19):5455-5461
A new series of CCR2 antagonists has been discovered that incorporates intramolecular hydrogen bonding as a strategy for rigidifying the scaffold. The structure-activity relationship was established through initial systematic modification of substitution pattern and chain length, followed by independent optimization of three different substituents (benzylamine, carboxamide, and benzamide). Several of the acyclic compounds display 10-30 nM binding affinity for CCR2. Moreover, these antagonists are able to block both MCP-1-induced Ca(2+) flux and monocyte chemotaxis, and are selective for binding to CCR2 over CCR1 and CCR3. 相似文献