全文获取类型
收费全文 | 108篇 |
免费 | 7篇 |
出版年
2020年 | 3篇 |
2016年 | 3篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 3篇 |
2012年 | 11篇 |
2011年 | 9篇 |
2010年 | 4篇 |
2009年 | 6篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 1篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 6篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1986年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1975年 | 1篇 |
1962年 | 1篇 |
1959年 | 1篇 |
1958年 | 1篇 |
1953年 | 1篇 |
1942年 | 1篇 |
1939年 | 1篇 |
1937年 | 1篇 |
1935年 | 1篇 |
1934年 | 1篇 |
1931年 | 1篇 |
1930年 | 2篇 |
1929年 | 2篇 |
1927年 | 1篇 |
1926年 | 1篇 |
1924年 | 1篇 |
排序方式: 共有115条查询结果,搜索用时 0 毫秒
1.
D N Harris M B Phillips I M Michel H J Goldenberg T E Steinbacher M L Ogletree S E Hall 《Prostaglandins》1986,31(4):651-667
7-Oxabicyclo[2.2.1]heptane analogs of prostaglandin (PG) H2 can act as thromboxane (Tx) A2 receptor antagonists or agonists, PGI2 and/or PGD2 receptor agonists, or exhibit a mixture of the above activities. SQ 28,852, a new analog with a hexyloxymethyl omega side chain, is a potent inhibitor of PG synthesis. SQ 28,852 inhibited collagen and arachidonic acid (AA)-induced platelet aggregation and TxB2 and PGE2 formation, but did not block platelet aggregation induced by ADP or the TxA2 mimics, 9,11-azo PGH2, SQ 26,655, and U-46,619. It also blocked conversion of AA to TxB2, PGE2, and 6-keto PGF1 alpha by microsomal preparations of human platelets, bovine seminal vesicles, and bovine aortas, respectively, but did not inhibit the conversion of PGH2 to TxA2 by the platelet microsomal preparation. SQ 28,852 (p.o.) protected mice against the lethal effects of AA (75 mg/kg, i.v.). The I50 values for SQ 28,852, indomethacin and aspirin were 0.025, 0.05 and 15 mg/kg, respectively. Neither SQ 28,852 nor indomethacin protected mice from death caused by 9,11-azo PGH2. SQ 28,852 (0.01 to 1 mg/kg, i.v.) inhibited AA-induced bronchoconstriction in anesthetized guinea pigs for at least 60 min. As an inhibitor of AA-induced bronchoconstriction, SQ 28,852 was 16- and 45-times more potent than indomethacin at 3 and 60 min after i.v. administration, respectively. SQ 28,852 did not inhibit bronchoconstriction induced by histamine or 9,11-azo PGH2, indicating its specificity of action in vivo. SQ 28,852 is the first example of a new class of cyclooxygenase inhibitors whose structure is similar to that of the naturally occurring endoperoxide, PGH2. 相似文献
2.
3.
Georg Steinbacher Otto Wettstein Josef Scholze Wolfgang Makatsch Kurt Bauer Harald Duchrow Klaus Warncke Peter Dancker E. Bezzel H. Remold und Helmut Sick 《Journal of Ornithology》1959,100(1):103-112
Ohne Zusammenfassung 相似文献
4.
The selective TxA2/PGH2 (TP) receptor antagonist, SQ 30,741, was used to test the hypothesis that TP-receptor activation contributes to the reactivity of airways and isolated trachea to endothelin-1 (ET-1). Dose-dependent contractions of guinea pig tracheal strips to ET-1 in vitro were unaffected by either SQ 30,741 (1 microM) or indomethacin (2.8 microM). In contrast, maximal bronchospastic responses (increases in airways resistance and decreases in dynamic lung compliance) of anesthetized guinea pigs to ET-1 (0.5 and 1.5 nmole/kg i.v.) in vivo were blocked greater than 90% by SQ 30,741 (1 mg/kg i.v.). Concurrent increases in arterial blood pressure and decreases in leukocyte counts induced by ET-1 were unaffected by SQ 30,741. In rats, ET-1 (1.5 nmole/kg i.v.) did not affect lung mechanics, but did cause biphasic blood pressure and leukopenia responses which were unaltered by SQ 30,741. These data demonstrate that there is considerable species variability in the bronchospastic response to ET-1, and that in guinea pigs, this response is caused predominantly by the activation of TP-receptors. 相似文献
5.
W.A. Schumacher T.E. Steinbacher S. Youssef M.L. Ogletree 《Prostaglandins & other lipid mediators》1992,44(5)
The effects of the novel TxA2/prostaglandin endoperoxide (TP) receptor antagonist BMS 180,291 on platelet reactivity was determined ex vivo in conscious African green monkeys. Platelet aggregation responses to U-46,619 were decreased 50% and 100% at 23 to 24 hrs after BMS 180,291 oral doses of 1 and 3 mg/kg, respectively. In addition to inhibiting aggregation, a 3 mg/kg oral dose of BMS 180,291 also produced an 11±3-fold shift to the right in the U-46,619 concentration-response relationship for platelet shape change at 24 hrs after dosing. When the 3 mg/kg oral dose was continued for 11 days, the shift in this concentration-response relationship increased to 26±10- and 93±30-fold at 24 hrs after the 8th and 11th doses, respectively. This progressive inhibition corresponds to 93±3 and 99±1% blockade of platelet TP-receptors responsible for shape change, respectively. Comparable levels of TP-receptor blockade have been previously correlated with antithrombotic and antiischemic activities of TP-receptor antagonists in vivo. Platelet reactivity to U-46,619 had completely recovered on the 7th day after the final dose of BMS 180,291, indicating effective elimination from the circulation over this interval. In separate experiments, a 3-mg/kg i.v. dose of BMS 180,291 produced only marginal and transient hemodynamic effects in anesthetized African green monkeys. Overall, these data demonstrate that BMS 180,291 given orally once a day produces a sustained and therapeutically-relevant level of TP-receptor antagonism. 相似文献
6.
The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs. 相似文献
7.
We isolated 20 anonymous nuclear loci (8556 bp in total) from the Taiwan Hwamei (Garrulax taewanus), an endemic songbird of Taiwan. A panel of nine to 15 individuals with unknown relationship was used to characterize polymorphism of these loci. We identified 46 single nucleotide polymorphic sites (SNPs) in 15 polymorphic loci. Frequency of SNPs was one per every 186 bp in average. Nucleotide diversity, θ, ranged from 0.00054 to 0.00371 per locus. We also tested cross‐species applicability of these loci on 17 species from eight different passerine families. All 20 loci could be successfully amplified (ranged from one to 16 species, mean = 7.9 species). 相似文献
8.
Kupke T Hernandez-Acosta P Steinbacher S Culianez-Macia FA 《The Journal of biological chemistry》2001,276(22):19190-19196
The Arabidopsis thaliana flavoprotein AtHAL3a is related to plant growth and salt and osmotic tolerance. AtHAL3a shows sequence homology to the bacterial flavoproteins EpiD and Dfp. EpiD, Dfp, and AtHAL3a are members of the homo-oligomeric flavin-containing Cys decarboxylase (HFCD) protein family. We demonstrate that AtHAL3a catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'-phosphopantetheine. This key step in coenzyme A biosynthesis is catalyzed in bacteria by the Dfp proteins. Exchange of His-90 of AtHAL3a for Asn led to complete inactivation of the enzyme. Dfp and AtHAL3a are characterized by a shortened substrate binding clamp compared with EpiD. Exchange of the cysteine residue of the conserved ACGD motif of this binding clamp resulted in loss of (R)-4'-phospho-N-pantothenoylcysteine decarboxylase activity. Based on the crystal structures of EpiD H67N with bound substrate peptide and of AtHAL3a, we present a model for the binding of (R)-4'-phospho-N-pantothenoylcysteine to AtHAL3a. 相似文献
9.
Bauer S Kemter K Bacher A Huber R Fischer M Steinbacher S 《Journal of molecular biology》2003,326(5):1463-1473
The essential redox cofactors riboflavin monophosphate (FMN) and flavin adenine dinucleotide (FAD) are synthesised from their precursor, riboflavin, in sequential reactions by the metal-dependent riboflavin kinase and FAD synthetase. Here, we describe the 1.6A crystal structure of the Schizosaccharomyces pombe riboflavin kinase. The enzyme represents a novel family of phosphoryl transferring enzymes. It is a monomer comprising a central beta-barrel clasped on one side by two C-terminal helices that display an L-like shape. The opposite side of the beta-barrel serves as a platform for substrate binding as demonstrated by complexes with ADP and FMN. Formation of the ATP-binding site requires significant rearrangements in a short alpha-helix as compared to the substrate free form. The diphosphate moiety of ADP is covered by the glycine-rich flap I formed from parts of this alpha-helix. In contrast, no significant changes are observed upon binding of riboflavin. The ribityl side-chain might be covered by a rather flexible flap II. The unusual metal-binding site involves, in addition to the ADP phosphates, only the strictly conserved Thr45. This may explain the preference for zinc observed in vitro. 相似文献
10.
Steinbacher S Kaiser J Eisenreich W Huber R Bacher A Rohdich F 《The Journal of biological chemistry》2003,278(20):18401-18407
2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway. As it is present in many pathogens and plants, but not in man, this pathway has attracted considerable interest as a target for novel antibiotics and herbicides. Fosmidomycin represents a specific high-affinity inhibitor of IspC. Very recently, its anti-malaria activity in man has been demonstrated in clinical trials. Here, we present the crystal structure of Escherichia coli IspC in complex with manganese and fosmidomycin at 2.5 A resolution. The (N-formyl-N-hydroxy)amino group provides two oxygen ligands to manganese that is present in a distorted octahedral coordination, whereas the phosphonate group is anchored in a specific pocket by numerous hydrogen bonds. Both sites are connected by a spacer of three methylene groups. The substrate molecule, 1-d-deoxyxylulose 5-phosphate, can be superimposed onto fosmidomycin, explaining the stereochemical course of the reaction. 相似文献