全文获取类型
收费全文 | 288篇 |
免费 | 11篇 |
国内免费 | 5篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 3篇 |
2017年 | 8篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 19篇 |
2012年 | 4篇 |
2011年 | 6篇 |
2010年 | 8篇 |
2009年 | 10篇 |
2008年 | 17篇 |
2007年 | 12篇 |
2006年 | 14篇 |
2005年 | 10篇 |
2004年 | 13篇 |
2003年 | 13篇 |
2002年 | 13篇 |
2001年 | 1篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 5篇 |
1982年 | 13篇 |
1981年 | 5篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 1篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 2篇 |
排序方式: 共有304条查询结果,搜索用时 15 毫秒
61.
《Bioorganic & medicinal chemistry》2020,28(23):115762
Human factor XIa (hFXIa) has emerged as an attractive target for development of new anticoagulants that promise higher level of safety. Different strategies have been adopted so far for the design of anti-hFXIa molecules including competitive and non-competitive inhibition. Of these, allosteric dysfunction of hFXIa’s active site is especially promising because of the possibility of controlled reduction in activity that may offer a route to safer anticoagulants. In this work, we assess fragment-based design approach to realize a group of novel allosteric hFXIa inhibitors. Starting with our earlier discovery that sulfated quinazolinone (QAO) bind in the heparin-binding site of hFXIa, we developed a group of two dozen dimeric sulfated QAOs with intervening linkers that displayed a progressive variation in inhibition potency. In direct opposition to the traditional wisdom, increasing linker flexibility led to higher potency, which could be explained by computational studies. Sulfated QAO 19S was identified as the most potent and selective inhibitor of hFXIa. Enzyme inhibition studies revealed that 19S utilizes a non-competitive mechanism of action, which was supported by fluorescence studies showing a classic sigmoidal binding profile. Studies with selected mutants of hFXIa indicated that sulfated QAOs bind in heparin-binding site of the catalytic domain of hFXIa. Overall, the approach of fragment-based design offers considerable promise for designing heparin-binding site-directed allosteric inhibitors of hFXIa. 相似文献
62.
A new iridoid glucoside, hygrophiloside, has been isolated from Hygrophila difformis. Hygrophiloside is apparently identical to the so-called ‘Cardanthera-Pseudoindican’. Its structure has been established by spectroscopic means and by reduction to isoaucubin. 相似文献
63.
T. Lockwich J. Chauthaiwale S. V. Ambudkar I. S. Ambudkar 《The Journal of membrane biology》1995,148(3):277-285
We have previously reported that rat parotid gland basolateral plasma membrane vesicles (BLMV) have a relatively high affinity Ca2+ transport pathway and an unsaturable Ca2+ flux component (Lockwich et al., 1994. J. Membrane Biol. 141:289–296). In this study, we have solubilized BLMV with octylglucoside (1.5%) and have reconstituted the solubilized proteins into proteoliposomes (PrL) composed of E. coli bulk phospholipids, by using a detergent dilution method. PrL exhibited 3–5-fold higher 45Ca2+ influx than control liposomes (without protein). Ca2+ uptake into PrL was dependent on the [protein] in PrL and steady state [Ca2+] in PrL was in equilibrium with external [Ca2+]. These data demonstrate that a passive, protein-mediated Ca2+ transport has been reconstituted from BLMV into PrL. 45Ca2+ influx into liposomes did not saturate with increasing [Ca2+] in the assay medium. In contrast, PrL displayed saturable 45Ca2+ influx and exhibited a single Ca2+ flux component with an apparent K
ca=242 ± 50.9 m and V
max=13.5 ± 1.14 nmoles Ca2+/mg protein/ minute. The K
ca of Ca2+-transport in PrL was similar to that of the high affinity Ca2+ influx component in BLMV while the V
max was about 4-fold higher. The unsaturable Ca2+ flux component was not detected in PrL. 45Ca2+ influx in PrL was inhibited by divalent cations in the order of efficacy, Zn2+>Mn2+>Co2+=Ni2+, and appeared to be more sensitive to lower concentrations of Zn2+ than in BLMV. Consistent with our observations with BLMV, the carboxyl group reagent N,N-dicyclohexylcarbodiimide (DCCD) inhibited the reconstituted Ca2+ transport in PrL. Importantly, in both BLMV and PrL, DCCD induced a 40–50% decrease in V
max of Ca2+ transport without an alteration in K
ca. These data strongly suggest that the high affinity, passive Ca2+ transport pathway present in BLMV has been functionally reconstituted into PrL. We suggest that this approach provides a useful experimental system towards isolation of the protein(s) involved in mediating Ca2+ influx in the rat parotid gland basolateral plasma membrane.We thank Dr. Bruce Baum for his constant support and encouragement. We also thank Ms. Grace Park and all our colleagues for their assistance during the course of this work. 相似文献
64.
Suresh V. Ambudkar 《Journal of bioenergetics and biomembranes》1995,27(1):23-29
The overexpression of the P-glycoprotein, theMDR1 gene product, has been linked to the development of resistance to multiple cytotoxic natural product anticancer drugs in certain cancers and cell lines derived from tumors. P-glycoprotein, a member of the ATP-binding cassette (ABC) superfamily of transporters, is believed to function as an ATP-dependent drug efflux pump with broad specificity for chemically unrelated hydrophobic compounds. We review here recent studies on the purification and reconstitution of P-glycoprotein to elucidate the mechanism of drug transport. P-glycoprotein from the human carcinoma multidrug resistant cell line, KB-V1, was purified by sequential chromatography on anion exchange followed by a lectin (wheat germ agglutinin) column. Proteoliposomes reconstituted with pure protein exhibited high levels of drug-stimulated ATPase activity as well as ATP-dependent [3H]vinblastine accumulation. Both the ATPase and vinblastine transport activities of the reconstituted P-glycoprotein were inhibited by vanadate. In addition, the vinblastine transport was inhibited by verapamil and daunorubicin. These studies provide strong evidence that the human P-glycoprotein functions as an ATP-dependent drug transporter. The development of the reconstitution system and the availability of recombinant protein in large amounts due to recent advances in overexpression of P-glycoprotein in a heterologous expression system should facilitate a better understanding of the function of this novel protein. 相似文献
65.
UDP-glucose:sterol glucosyltransferase: cloning and functional expression in Escherichia coli/ 总被引:4,自引:0,他引:4
Warnecke Dirk C. Baltrusch Martina Buck Friedrich Wolter Frank P. Heinz Ernst 《Plant molecular biology》1997,35(5):597-603
Steryl glucosides are characteristic lipids of plant membranes. The biosynthesis of these lipids is catalyzed by the membrane-bound UDP-glucose:sterol glucosyltransferase (EC 2.4.1.173). The purified enzyme (Warnecke and Heinz, Plant Physiol 105 (1994): 1067–1073) has been used for the cloning of a corresponding cDNA from oat (Avena sativa L.). Amino acid sequences derived from the amino terminus of the purified protein and from peptides of a trypsin digestion were used to construct oligonucleotide primers for polymerase chain reaction experiments. Screening of oat and Arabidopsis cDNA libraries with amplified labeled DNA fragments resulted in the isolation of sterol glucosyltransferase-specific cDNAs with insert lengths of ca. 2.3 kb for both plants. These cDNAs encode polypeptides of 608 (oat) and 637 (Arabidopsis) amino acid residues with molecular masses of 66 kDa and 69 kDa, respectively. The first amino acid of the purified oat protein corresponds to the amino acid 133 of the deduced polypeptide. The absence of these N-terminal amino acids reduces the molecular mass to 52 kDa, which is similar to the apparent molecular mass of 56 kDa determined for the purified protein. Different fragments of these cDNAs were expressed in Escherichia coli. Enzyme assays with homogenates of the transformed cells exhibited sterol glucosyltransferase activity. 相似文献
66.
Two iridoid glycosides have been isolated from Viburnum betulifolium. Viburnalloside, the major leaf glycoside, is composed of an iridoid aglucone acylated at C-1 with isovaleric acid and with a di-O-acetyl-β-D-allopyranosyl moiety attached through a glycosidic bond to C-11. Decapetaloside (10-hydroxyiridodial glucoside) has been isolated from the bark. The structure and absolute configuration of viburnalloside have been established by spectroscopic means, and those of decapetaloside by chemical correlation with adoxoside. 相似文献
67.
Besides the known glucoside jasminin and an unidentified glucoside, two new secoiridoid glucosides,jasmoside and jasmesoside have been isolated from the leaves of Jasminum mesnyi and their structures elucidated. 相似文献
68.
Fujio Murai Motoko Tagawa Satoko Matsuda Tohru Kikuchi Shinichi Uesato Hiroyuki Inouye 《Phytochemistry》1985,24(10):2329-2335
Twp new secoiridoid glucosides, abeliosides A and B, were isolated along with cantleyoside and sylvestroside II from Abelia grandiflora. On the basis of spectral and chemical evidence, these new glucosides were identified as esters of secologanic acid with an iridoid lactone which may arise from loganin. Cantleyoside was also isolated from A. spathulata and A. serrata. 相似文献
69.
Siddabasave Gowda B. Gowda Seigo Usuki Mostafa A. S. Hammam Yuta Murai Yasuyuki Igarashi Kenji Monde 《Journal of lipid research》2016,57(2):325-331
Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond β-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield. 相似文献
70.
The non-ionic detergent octyl glucoside solubilizes a substantial amount of Streptococcus faecalis membrane protein without loss of the monitored enzyme activities. A secondary detergent, dioctanoyl phosphatidylcholine, appears to increase the yield of solubilized material. In addition, the effect of ionic strength indicates that it may be possible to selectively extract groups of membrane proteins by their characteristic solubility at different ionic strengths.The solubilized membrane-associated enzymes, ATPase and NADH dehydrogenase enter polyacrylamide gels as distinct species. Electrophoretic studies suggest that there are two membrane-associated ATPases in the Streptococcus faecalis, one which dissociates from the membrane in the absence of Mg2+ ions and the other which remains particulate until solubilized by detergents.Octyl glucoside can be easily removed from a solution containing solubilized proteins and lipid by dialysis. 相似文献