排序方式: 共有58条查询结果,搜索用时 15 毫秒
51.
Somoza JR Ho JD Luong C Ghate M Sprengeler PA Mortara K Shrader WD Sperandio D Chan H McGrath ME Katz BA 《Structure (London, England : 1993)》2003,11(9):1123-1131
Hepsin is an integral membrane protein that may participate in cell growth and in maintaining proper cell morphology and is overexpressed in a number of primary tumors. We have determined the 1.75 A resolution structure of the extracellular component of human hepsin. This structure includes a 255-residue trypsin-like serine protease domain and a 109-residue region that forms a novel, poorly conserved, scavenger receptor cysteine-rich (SRCR) domain. The two domains are associated with each other through a single disulfide bond and an extensive network of noncovalent interactions. The structure suggests how the extracellular region of hepsin may be positioned with respect to the plasma membrane. 相似文献
52.
Rai R Kolesnikov A Sprengeler PA Torkelson S Ton T Katz BA Yu C Hendrix J Shrader WD Stephens R Cabuslay R Sanford E Young WB 《Bioorganic & medicinal chemistry letters》2006,16(8):2270-2273
Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine scaffold. 相似文献
53.
Young WB Mordenti J Torkelson S Shrader WD Kolesnikov A Rai R Liu L Hu H Leahy EM Green MJ Sprengeler PA Katz BA Yu C Janc JW Elrod KC Marzec UM Hanson SR 《Bioorganic & medicinal chemistry letters》2006,16(7):2037-2041
Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented. 相似文献
54.
Riggs JR Kolesnikov A Hendrix J Young WB Shrader WD Vijaykumar D Stephens R Liu L Pan L Mordenti J Green MJ Sukbuntherng J 《Bioorganic & medicinal chemistry letters》2006,16(8):2224-2228
We have developed a series of potent and selective factor VIIa inhibitors based on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid scaffold. These amidine-containing compounds have low oral bioavailability. Herein, we describe our efforts to improve the oral bioavailability of the parent amidine via a prodrug strategy where the amidine basicity and polarity were reduced with either an alkoxy-amidine or a carbamate prodrug. 相似文献
55.
Adrian M. Shrader Stuart L. Pimm Rudi J. van Aarde 《Biodiversity and Conservation》2010,19(8):2235-2245
Elephant are increasing across some areas of Africa leading to concerns that they may reduce woodlands through their feeding.
Droughts may help limit elephant numbers, but they are generally both episodic and local. To explore more general impacts
of rainfall, we examine how its annual variation influences elephant survival across ten sites. These sites span an almost
coast-to-coast transect of southern Africa that holds the majority of the ~500,000 remaining savanna elephants. Elephants
born in high rainfall years survive better than elephants born in low rainfall years. The relationship is generally weak,
except at the two fenced sites, where rainfall greatly influenced juvenile survival. In these two sites, there are also extensive
networks of artificial water. Rainfall likely affects elephant survival through its influence on food. The provision of artificial
water opens new areas for elephants in the dry season, while fencing restricts their movements in the wet season. We conclude
that the combination of these factors makes elephant survival more susceptible to reductions in rainfall. As a result, elephants
living in enclosed reserves may be the first populations to feel the impacts of global warming which will decrease average
rainfall and increase the frequency of droughts. A way to prevent these elephants from damaging the vegetation within these
enclosed parks is for managers to reduce artificial water sources or, whenever practical, to remove fences. 相似文献
56.
Prevalence, intensity and pathogenesis of Lernaea cyprinacea (anchorworm) in stocked rainbow trout (Oncorhynchus mykiss) fingerlings were monitored annually for 4 yr (1981 to 1984) in East Canyon Reservoir, Utah (USA). Anchorworms were first detected in midsummer each year and were most abundant in the fall. The mean parasite intensity was highest in October 1982 (19 anchorworms per fish); in other years, maximum density was 7 to 9. The dorsal and caudal areas of the fish were the most heavily parasitized. The histological response to parasite attachment included an infectious granuloma similar to that reported in other fish hosts. Bacteria were not found in the kidneys of fish before stocking, but afterward bacteria that were presumptively identified as belonging to the genus Aeromonas, were found in the kidneys of up to 45% of the parasitized fish. Most (94%) anglers noticed the anchorworms, but few (8%) discarded parasitized fish. Some 28% used special cleaning techniques to prepare fish but 49% did nothing special to clean them. Lernaeosis probably had little effect on the fishery management goals for the reservoir. 相似文献
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58.
The identification of some human metabolites of norgestrel, a new progestational agent 总被引:1,自引:0,他引:1
D C DeJongh J D Hribar P Littleton K Fotherby R W Rees S Shrader T J Foell H Smith 《Steroids》1968,11(5):649-666
Norgestrel 1 (racemic 13-beta-ethyl-17-alpha-hydroxygon-4-en-3-one) a progestational agent with an angular ethyl group between Rings C and D, was studied by mass spectrometry to discover its structural characteristics. Synthesis of postulated metabolites of Norgestrel 1 for use in identification is described and structural formulas are given. Urine was used as a source to characterize fractions via mass spectra, and the fraction spectra are listed. The major metabolite was 13-beta-ethyl-17-alpha-ethynl-5-beta-gonan-3-alpha-1m-beta-diol 8c. 相似文献