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C Chen M Kano A Abeliovich L Chen S Bao JJ Kim K Hashimoto RF Thompson S Tonegawa 《Canadian Metallurgical Quarterly》1995,83(7):1233-1242
It is generally believed that a smooth execution of a compound movement, or motor coordination, requires learning of component movements as well as experience-based refinement of the motor program as a whole. PKC gamma mutant mice display impaired motor coordination but intact eyeblink conditioning, a form of component movement learning. Cerebellar long-term depression, a putative cellular mechanism for component motor learning, is also unimpaired. Thus, PKC gamma mutant mice are defective in refinement of the motor program. In the accompanying paper, we demonstrate that innervation of multiple climbing fibers onto Purkinje cells persists in adulthood in these mutant mice. We propose that this defective elimination of surplus climbing fibers underlies motor discoordination. 相似文献
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FG Salituro CT Baker JJ Court DD Deininger EE Kim B Li PM Novak BG Rao S Pazhanisamy MD Porter WC Schairer RD Tung 《Canadian Metallurgical Quarterly》1998,8(24):3637-3642
A set of HIV protease inhibitors represented by compound 2 has previously been described. Structural and conformational analysis of this compound suggested that conformational restriction of the P1/P2 portion of the molecule could lead to a novel set of potent protease inhibitors. Thus, probe compounds 3-7 were designed, synthesized, and found to be potent inhibitors of HIV protease. 相似文献
1000.
JJ Martocchio 《Canadian Metallurgical Quarterly》1994,79(6):819-825
Octreotide is labeled with fluorine-18 as a potential radiopharmaceutical for quantitative in vivo mapping of somatostatin receptors. [18F]-fluoroacylation is achieved with n.c.a. 2-[18F]fluoropropionic acid 4-nitrophenylester which is reacted with epsilon-Boc-Lys5-octreotide. After deprotection the desired N alpha-[18F]fluoropropionylated octreotide ([18F]SDZ 223-228) is obtained. Final HPLC purification gives rise to radiochemical yields of 65 +/- 5% based on the fluoroacylation agent. Binding experiments using rat cortex membranes indicate an affinity for somatostatin receptors of pKi = 8.6 +/- 0.2. The biological activity of this SRIF analog is demonstrated by the inhibition of growth hormone release from cultured pituitary cells. The pIC50 in this test system is 8.75, indicating full biological activity. Biodistribution studies with NMRI mice show predominantly renal excretion, rapid blood clearance and only negligible bone activity, i.e. formation of free fluoride. 相似文献