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排序方式: 共有180条查询结果,搜索用时 34 毫秒
101.
Coleman PJ Schreier JD Cox CD Fraley ME Garbaccio RM Buser CA Walsh ES Hamilton K Lobell RB Rickert K Tao W Diehl RE South VJ Davide JP Kohl NE Yan Y Kuo L Prueksaritanont T Li C Mahan EA Fernandez-Metzler C Salata JJ Hartman GD 《Bioorganic & medicinal chemistry letters》2007,17(19):5390-5395
3,5-diaryl-4,5-dihydropyrazoles were discovered to be potent KSP inhibitors with excellent in vivo potency. These enzyme inhibitors possess desirable physical properties that can be readily modified by incorporation of a weakly basic amine. Careful adjustment of amine basicity was essential for preserving cellular potency in a multidrug resistant cell line while maintaining good aqueous solubility. 相似文献
102.
Brnardic EJ Garbaccio RM Fraley ME Tasber ES Steen JT Arrington KL Dudkin VY Hartman GD Stirdivant SM Drakas BA Rickert K Walsh ES Hamilton K Buser CA Hardwick J Tao W Beck SC Mao X Lobell RB Sepp-Lorenzino L Yan Y Ikuta M Munshi SK Kuo LC Kreatsoulas C 《Bioorganic & medicinal chemistry letters》2007,17(21):5989-5994
The development of 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones as inhibitors of Chk1 kinase is described. Introduction of a fused ring at the C7/C8 positions of the pyrazoloquinolinone provided an increase in potency while guidance from overlapping inhibitor bound Chk1 X-ray crystal structures contributed to the discovery of a potent and solubilizing propyl amine moiety in compound 52 (Chk1 IC(50)=3.1 nM). 相似文献
103.
Lúcia de Paula Célio L Silva Daniela Carlos Camila Matias-Peres Carlos A Sorgi Edson G Soares Patrícia RM Souza Carlos RZ Bladés Fábio CS Galleti Vânia LD Bonato Eduardo DC Gonçalves Érika VG Silva Lúcia H Faccioli 《Genetic vaccines and therapy》2007,5(1):1-7
The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs. 相似文献
104.
Ilaria Callegari Mika Schneider Giuliano Berloffa Tobias Mühlethaler Sebastian Holdermann Edoardo Galli Tim Roloff Renate Boss Laura Infanti Nina Khanna Adrian Egli Andreas Buser Gert Zimmer Tobias Derfuss Nicholas S R Sanderson 《EMBO reports》2022,23(7)
To investigate the class‐dependent properties of anti‐viral IgM antibodies, we use membrane antigen capture activated cell sorting to isolate spike‐protein‐specific B cells from donors recently infected with SARS‐CoV‐2, allowing production of recombinant antibodies. We isolate 20, spike‐protein‐specific antibodies of classes IgM, IgG, and IgA, none of which shows any antigen‐independent binding to human cells. Two antibodies of class IgM mediate virus neutralization at picomolar concentrations, but this potency is lost following artificial switch to IgG. Although, as expected, the IgG versions of the antibodies appear to have lower avidity than their IgM parents, this is not sufficient to explain the loss of potency. 相似文献
105.
P. M. Guerin H. R. Buser M. Tóth E. Höbaus A. Schmid H. Arn 《Entomologia Experimentalis et Applicata》1986,40(2):137-140
Female sex pheromone gland extracts of Sparganothis pilleriana contain E-9-dodecenyl acetate, E-11-tetradecenyl acetate, Z-11-tetradecenyl acetate and saturated acetates of 12 to 24 carbons. Addition of E-9-dodecen-1-ol to the blend of the three unsaturated acetates is necessary to obtain maximum male catch.
Zusammenfassung Weibliche Sexualpheromondrüsen des Spring-wurmwicklers S. pilleriana enthalten E-9-Dodecenylacetat, E-11-Tetradecenylacetat und Z-11-Tetradecenylacetat neben gesättigten Acetaten mit 12 bis 24 Kohlenstoffeinheiten. Die beste Lockwirkung auf Männchen des Springwurmwicklers wird erzielt, wenn man dem Gemisch der drei ungesättigten Acetate E-9-Dodecen-1-ol zufügt, welches als elektrophysiologisch hoch wirksam bekannt ist, aber in den Drüsen nicht nachgewiesen werden konnte.相似文献
106.
107.
The stoichiometry of cytochrome b559 (one or two copies) per reaction center of photosystem II (PSII) has been the subject of considerable debate. The molar ratio of cytochrome b559 has a number of significant implications on our understanding of the functional role of cytochrome b559, the mechanism of electron donation in PSII, and the stoichiometry of the other redox-active, reaction center components. We have reinvestigated the stoichiometry of cytochrome b559 in PSII-enriched and thylakoid membranes, using differential absorbance and electron paramagnetic resonance spectroscopies. The data from both quantitation procedures strongly indicate only one copy of cytochrome b559 per reaction center in PSII-enriched membranes and also suggest one copy of cytochrome b559 per reaction center in thylakoid membranes. 相似文献
108.
Sarah L. Hoffmann Thaddaeus J. Buser Marianne E. Porter 《Journal of morphology》2020,281(11):1501-1516
Sharks vary greatly in morphology, physiology, and ecology. Differences in whole body shape, swimming style, and physiological parameters have previously been linked to varied habitat uses. Pectoral fin morphology has been used to taxonomically classify species and hypotheses on the functional differences in shape are noted throughout the literature; however, there are limited comparative datasets that quantify external and skeletal morphology. Further, fins were previously categorized into two discrete groups based on the amount of skeletal support present: (a) aplesodic, where less than half of the fin is supported and (b) plesodic where greater than half of the fin is supported. These discrete classifications have been used to phylogenetically place species, though the methodology of classification is infrequently described. In this study, we sampled fins from 18 species, 6 families, and 3 orders, which were also grouped into five ecomorphotype classifications. We examined the external morphology, extent of skeletal support, and cross-sectional shape of individual cartilaginous elements. Using phylogenetic comparative methods, we show that fin shape does not differ significantly between ecomorphotypes, suggesting there may be some mechanical constraint. However, we find that the internal anatomy of the fin does vary significantly between ecomorphotypes, especially the extent and distribution of calcification of skeletal support, suggesting that the superficial similarity of fin shapes across ecomorphotypes may belie differences in function. Finally, we find that a number of morphological variables such as number of radials, radial calcification and shape, and fin taper all correlate with the extent of skeletal support. Within these morphospaces, we also describe that some orders/families tend to occupy certain areas with limited overlap. While we demonstrate that there is some mechanical constraint limiting external variations in shark pectoral fin morphology, there are compounding differences in skeletal anatomy that occur within ecomorphotypes which we propose may affect function. 相似文献
109.