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排序方式: 共有438条查询结果,搜索用时 31 毫秒
1.
2.
Susanne Berglund Bryan J. Egner Henrik Gradén Joakim Gradén David G.A. Morgan Tord Inghardt Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2009,19(15):4268-4273
Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration. 相似文献
3.
James M. Chen Rosalyn Grad Regina Monaco Matthew R. Pincus 《Journal of Protein Chemistry》1996,15(1):11-16
rap-1A, an anti-oncogene-encoded protein, is aras-p21-like protein whose sequence is over 80% homologous to p21 and which interacts with the same intracellular target proteins and is activated by the same mechanisms as p21, e.g., by binding GTP in place of GDP. Both interact with effector proteins in the same region, involving residues 32–47. However, activated rap-1A blocks the mitogenic signal transducing effects of p21. Optimal sequence alignment of p21 and rap-1A shows two insertions of rap-1A atras positions 120 and 138. We have constructed the three-dimensional structure of rap-1A bound to GTP by using the energy-minimized three-dimensional structure ofras-p21 as the basis for the modeling using a stepwise procedure in which identical and homologous amino acid residues in rap-1A are assumed to adopt the same conformation as the corresponding residues in p21. Side-chain conformations for homologous and nonhomologous residues are generated in conformations that are as close as possible to those of the corresponding side chains in p21. The entire structure has been subjected to a nested series of energy minimizations. The final predicted structure has an overall backbone deviation of 0.7 å from that ofras-p21. The effector binding domains from residues 32–47 are identical in both proteins (except for different side chains of different residues at position 45). A major difference occurs in the insertion region at residue 120. This region is in the middle of another effector loop of the p21 protein involving residues 115–126. Differences in sequence and structure in this region may contribute to the differences in cellular functions of these two proteins. 相似文献
4.
Soils contain two different activities for oxidation of hydrogen 总被引:1,自引:0,他引:1
Abstract Hydrogen oxidation rates were measured in a neutral compost soil and an acidic sandy loam at H2 mixing ratios of 0.01 to 5000 ppmv. The kinetics were biphasic showing two different K m values for H2 , one at about 10–40 nM dissolved H2 , the other at about 1.2–1.4 μM H2 . The low- K m activity was less sensitive to chloroform fumigation than the high- K m activity. If sterile soil was amended with Paracoccus denitrificans or a H2 -oxidizing strain isolated from compost soil, it exhibited only a high- K m (0.7–0.9 μM) activity. It also failed to utilize H2 mixing ratios below a threshold of 1.6–3.0 ppmv H2 (160–300 mPa). A similar result was obtained when fresh soil samples were suspended in water, and H2 oxidation was determined from the decrease of dissolved H2 . However, H2 was again utilized to mixing ratios lower than 0.05 ppmv, if the supernatant of the soil suspension or the settled soil particles were dried onto sterile soil or purified quarz sand. Obviously, soils contain two different activities for oxidation of H2 : (1) a high- K m , high-threshold activity which apparently is due to aerobic H2 -oxidizing bacteria, and (2) a low- K m , low-threshold activity whose origin is unknown but presumably is due to soil enzymes. 相似文献
5.
Rolf Altenburger Sibylle Abarzua Rainer Callies L. Horst Grimme Adalbert Mayer Dieter Leibfritz 《Archives of microbiology》1991,156(6):471-476
Cultures of the cyanobacterium Microcystis firma show rhythmic uptake and release of ammonia under conditions of carbon limitation. The massive removal of ammonia from the medium during the first light phase has little impact on the intracellular pH: a pH shift of less than 0.2 U towards the alkaline can be measured by in vivo 31P NMR. Furthermore, the energy status of the cells remains regulated. In vivo 15N NMR of M. firma, cultivated either with labelled nitrate or ammonia as the sole nitrogen source, reveals only gradual differences in the pool of free amino acids. Additionally both cultivation types show -aminobutyric acid, acid amides and yet unassigned secondary metabolites as nitrogen storing compounds. Investigating the incorporation of nitrogen under carbon limitation, however, only the amide nitrogen of glutamine is found permanently labelled in situ. While transamination reactions are blocked, nitrate reduction to ammonia can still proceed. Cation exchange processes in the cell wall are considered regarding the ammonia disappearance in the first phase, and the control of ammonia uptake is discussed with respect to the avoidance of intracellular toxification.Abbreviations GABA
-aminobutyric acid
- GOGAT
glutamate synthase
- GS
glutamine synthetase
- MDP
methylene diphosphonate
- MOPSO
3-(N-morpholino)-2-hydroxy-propanesulfonic acid
- NDPS
nucieoside diphosphosugars
- NOE
nuclear Overhauser effect
- NMR
nuclear magnetic resonance
For convenience, the term ammonia is used throughout to denote ammonia or ammonium ion when there is no good evidence as to which chemical species is involved 相似文献
6.
Of the nine species of Tropodiaptomus occurring in Equatorial East Africa, seven are redescribed and figured in great detail. Their relationships are discussed. A primary homonym is eliminated, and types are indicated wherever possible. 相似文献
7.
S F Quan R J Lemen M L Witten D L Sherrill R Grad R E Sobonya C G Ray 《Journal of applied physiology》1990,69(6):2034-2042
We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection. 相似文献
8.
9.
dos Santos Silva Edinaldo N. Kakkassery Francy K. Maas Sibylle Dumont Henri J. 《Hydrobiologia》1994,288(2):119-128
Calanoid copepods, belonging to the new genus and species Keraladiaptomus rangareddyi, were collected from temporary ponds in Kerala State, India. The new genus belongs to the family Diaptomidae, subfamily Diaptominae. It is described in detail and its affinity to the related genera, Arctodiaptomus Kiefer, 1932 and Eodiaptomus Kiefer, 1932, discussed. 相似文献
10.
Wound-induced and developmental activation of a poplar tree chitinase gene promoter in transgenic tobacco 总被引:5,自引:0,他引:5
Howard R. G. Clarke John M. Davis Sibylle M. Wilbert Harvey D. Bradshaw Jr. Milton P. Gordon 《Plant molecular biology》1994,25(5):799-815
Wounding hybrid poplar (Populus trichocarpa × P. deltoides) trees results in the expression of novel wound-inducible (win) mRNAs thought to encode proteins involved in defense against pests and pathogens. Members of thewin6 gene family encode acidic multi-domain chitinases, with combined structure and charge characteristics that differ from previously described chitinases.Win6 expression has been shown to occur in pooled unwounded leaves of a wounded (on multiple leaves) poplar plant. Here we demonstrate that wounding a single leaf induceswin6 expression locally, in the wounded leaf, and remotely, in specific unwounded leaves with strong vascular connections to the wounded leaf. We also demonstrate that awin6 promoter--glucuronidase (GUS) gene fusion (win6-GUS) responds to wounding locally and remotely in transgenic tobacco. These data indicate that the poplarwin6 promoter has regulatory elements that are responsive to wound signals in the heterologous host. In addition,win6-GUS is developmentally activated in unwounded young leaves and floral tissues of transgenic tobacco. Similar developmental expression patterns are found to occur forwin6 in poplar trees, demonstrating that a herbaceous plant can serve as a host for woody tree transgene analysis and can accurately predict expression patterns in tree tissues (e.g. flowers) that would be difficult to study in free-living trees. 相似文献