全文获取类型
收费全文 | 134篇 |
免费 | 15篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 3篇 |
基础医学 | 40篇 |
口腔科学 | 1篇 |
临床医学 | 17篇 |
内科学 | 34篇 |
神经病学 | 4篇 |
特种医学 | 10篇 |
外科学 | 9篇 |
预防医学 | 3篇 |
药学 | 13篇 |
肿瘤学 | 13篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 3篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 6篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 5篇 |
2007年 | 7篇 |
2006年 | 5篇 |
2005年 | 13篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 13篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1997年 | 3篇 |
1995年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1937年 | 1篇 |
1925年 | 1篇 |
1911年 | 1篇 |
1904年 | 1篇 |
排序方式: 共有149条查询结果,搜索用时 93 毫秒
51.
Linda Thunberg Shalini Andersson Stig Allenmark J?rgen Vessman 《Journal of pharmaceutical and biomedical analysis》2002,27(3-4):431-439
The present work is focused on the resolution of ten racemates, in order to study their chiroptical properties and to test the validity of the requirement specified in the European Pharmacopeia (EP) for demonstrating that a drug entity is a racemate. This work shows that the optical purity of enantiomers and non racemic mixtures of a number of compounds can be determined more accurately by circular dichroic (CD) spectroscopy than by a measurement of the angle of rotation (AoR), the EP requirement. Using only the AoR, some of the racemates could not be distinguished from the enantiomers. CD spectroscopy or chiral chromatography should, therefore, be the technique of choice in the determination of optical purity of a chiral compound, especially for those exhibiting low AoR. 相似文献
52.
53.
54.
55.
U Lindahl G Bckstrm M Hk L Thunberg L A Fransson A Linker 《Proceedings of the National Academy of Sciences of the United States of America》1979,76(7):3198-3202
Heparin preparations from pig intestinal mucosa and from bovine lung were separated by chromatography on antithrombin-Sepharose into a high-affinity fraction (with high anticoagulant activity) and a low-affinity fraction (with low anticoagulant). Antithrombin-binding heparin fragments (12-16 monosaccharide units) were prepared, either by digesting a high-affinity heparin-antithrombin complex with bacterial heparinase or by partial deaminative cleavage of the unfractionated polysaccharide with nitrous acid followed by affinity chromatography on immobilized antithrombin. Compositional analysis based on separation and identification of deamination products reduced with sodium boro[3H]hydride showed that nonsulfated L-iduronic acid occurred in larger amounts in high-affinity heparin than in low-affinity heparin; furthermore, this component was concentrated in the antithrombin-binding regions of the high-affinity heparin molecules, amounting to approximately one residue per binding site. It is suggested that nonsulfated L-iduronic acid is essential for the anticoagulant activity of heparin. The location of the non-sulfated uronic acid in the antithrombin-binding site was determined by periodate oxidation of antithrombin-binding fragments containing a terminal 2,5-anhydro-D-[1-3H]mannitol unit. Tentative structures for antithrombin-binding sequences in heparin are proposed, including some structural variants believed to be compatible with, but not required for, activity. 相似文献
56.
57.
An earlier study of the metabolism of pentachlorophenol has shown that a metabolite, tetrachloro-p-hydroquinone, possessed pronounced inhibitory action on the activity of -glucuronidase from bacterial origin. Several other chlorinated hydroquinones and benzoquinones have now been studied with regard to their ability to inhibit -glucuronidase of various origin in vitro and in vivo.All the studied chlorinated hydroquinones and benzoquinones were found to be potent inhibitors of -glucuronidase of bacterial origin. D-glucaric acid-1.4-lactone was included for comparison and was found to be less active than the other studied compounds. The inhibition was found to be competitive in nature.No inhibitory effect of the benzo- and hydroquinones studied in vitro or in vivo could be demonstrated on -glucuronidase from livers. The result calls for precaution when using bacterial -glucuronidase to split urinary conjugates of glucuronic acid.
Zusammenfassung Eine frühere Studie des Metabolismus von Pentachlorphenol hat gezeigt, daß ein Metabolit, Tetrachlor-p-hydrochinon, eine ausgesprochene Hemmwirkung auf die Aktivität der Bakterien--Glucuronidase besitzt. Verschiedene andere chlorierte Hydrochinone und Benzochinone sind jetzt auf ihre Fähigkeit, -Glucuronidase anderen Ursprungs zu hemmen, in vitro und in vivo, untersucht worden.Alle die untersuchten chlorierten Hydrochinone und Benzochinone zeigten sich als starke Hemmer der Bakterien -Glucuronidase. D-Glucarsäure-1.4-Lakton wurde zum Vergleich einbezogen und wurde weniger aktiv als die anderen Verbindungen befunden. Die Hemmung war kompetitiver Art.Kein Hemmungseffekt von Hydro-oder Benzochinonen konnte in vitro oder in vivo auf Leber--Glucuronidase gezeigt werden. Das Resultat mahnt zur Vorsieht, wenn Bakterien -Glucuronidase zur Spaltung von Harnkonjugaten der Glucuronsäure angewandt wird.相似文献
58.
Tuula Thunberg Ulf G. Ahlborg Helen Håkansson Cilla Krantz Mats Monier 《Archives of toxicology》1980,45(4):273-285
The effect of various dietary sources of vitamin A on liver storage of retinol has been investigated in Sprague-Dawley rats treated with single oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): 0, 0.1, 1.0, or 10 g · kg–1. Each dose group consisted of 3 subgroups, each comprising 10 rats which received a diet with normal, low or high retinol content. The animals were killed 4 weeks after TCDD administration. Analyses of retinol were performed by high pressure liquid chromatography and glucurono-syltransferase activities were determined spectrophotometrically. A dose-dependent decrease in hepatic storage of retinol was evident. The high retinol diet did not fully compensate for the reduction caused by the highest TCDD-dose. Glucuronosyltransferase activity increased directly in relation to the TCDD-dose but in inverse proportion to the retinol content of the diet.
Zusammenfassung Der Einfluß verschieden hoher Gaben von Vitamin A auf die Retinolspeicherung der Leber bei Sprague-Dawley Ratten, die unterschiedliche Dosen von 2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD) erhalten haben, ist untersucht worden.Jede Dosierungsgruppe bestand aus drei Untergruppen, die jeweils eine Kost mit normalem, mit erniedrigtem und mit erhöhtem Retinolgehalt verabreicht bekamen. Vier Wochen nach der TCDD-Zufuhr wurden Retinolgehalt und Glucuronosyl-Transferase-Aktivität mit Hilfe der Hoch-druckflüssigkeitschromatographie bzw. spektrofotometrisch bestimmt. Eine dosierungsabhängige Abnahme der Retinolspeicherung in der Leber war deutlich. Die Hochretinolkost war nicht fähig, die durch die höchste TCDD-Gabe verursachte Senkung ganz auszugleichen. Die Glucuronosyl-Transferase-Aktivität wuchs linear mit der TCDD-Dosis, war aber auch umgekehrt proportional mit dem Retinolgehalt der Kost.相似文献
59.
Pentachlorophenol has earlier been shown to be metabolized in mammals to tetrachloro-p-hydroquinone. The metabolite possesses pronounced inhibitory activity on bacterial -glucuronidase but not on -glucuronidase from liver. Indirect evidence for the occurrence of both pentachlorophenol and tetrachloro-p-hydroquinone as conjugates with glucuronic acid in the urine from pentachlorophenol-treated rats is now presented. Bovine liver -glucuronidase has been utilized to split the conjugates present.The in vivo metabolism of pentachlorophenol has also been studied in rats treated with phenobarbital and -diethylaminoethyldiphenyl propylacetate (SKF 525-A). In vitro metabolism has been studied using liver microsomes from rats pretreated with phenobarbital. Quantitative analysis of the compounds occurring in extracts of urine or extracts from the microsomal incubates was performed by means of mass fragmentography. Pretreatment with phenobarbital increased the metabolism of pentachlorophenol to tetrachloro-p-hydroquinone both in vivo and in vitro. SKF 525-A, however, inhibited the metabolism in vitro but enhanced the metabolism in vivo when given less frequently than every 6th h. Dechlorination of pentachlorophenol is mediated by microsomal enzymes that can be induced by phenobarbital. SKF 525-A does not inhibit the dechlorination in vivo but does so in vitro.
Zusammenfassung Wie in früheren Versuchen gezeigt worden ist, wird Pentachlorphenol bei Säugern zu Tetrachlor-p-Hydrochinon metabolisiert. Dieser Metabolit wirkt ausgeprägt hemmend auf Bakterien--Glucuronidase, aber nicht auf Leber--Glucuronidase. Ein indirekter Beweis für das Vorkommen von sowohl Pentachlorphenol als auch Tetrachlor-p-Hydrochinon als Konjugate mit Glucuronsäure im Harn von pentachlorphenolbehandelten Ratten wird nun vorgelegt. Zur Spaltung der gegenwärtigen Konjugate wurde Rinderleber--Glucuronidase benutzt.Der in vivo-Abbau von Pentachlorphenol wurde auch an mit phenobarbital und mit -Diäthylaminoäthyl-Diphenyl-Propylacetat (SKF 525-A) behandelten Ratten untersucht.Beim Studium des in vitro-Abbaus wurden Lebermikrosomen von mit Phenobarbital behandelten Ratten benutzt. Phenobarbital steigerte die Umwandlung in Tetrachlor-p-Hydrochinon sowohl in vivo als auch in vitro. SKF 525-A verzögerte indessen den in vitro-Umsatz, steigerte ihn jedoch in vivo, wenn weniger oft als alle 6 Std gegeben. Die Untersuchung zeigt also, daß die Entchlorung von Pentachlorphenol durch Mikrosomenenzyme vermittelt wird, die durch phenobarbital angeregt werden können. SKF 525-A hemmt die Entchlorung nicht in vivo, wohl aber in vitro.相似文献
60.
Gafvelin G Thunberg S Kronqvist M Grönlund H Grönneberg R Troye-Blomberg M Akdis M Fiebig H Purohit A Horak F Reisinger J Niederberger V Akdis CA Cromwell O Pauli G Valenta R van Hage M 《International archives of allergy and immunology》2005,138(1):59-66
BACKGROUND: Recently, recombinant hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, were used to treat birch-pollen-allergic patients in a double-blind, placebo-controlled, multi-centre immunotherapy study. The aim of this study was to evaluate the effects of vaccination with aluminium-hydroxide-adsorbed recombinant Bet v 1 derivatives versus placebo on T-cell, cytokine and antibody responses in a subgroup of patients. METHODS: Blood was drawn from patients of the Swedish centre (n = 27; rBet v 1 fragments: n = 10; rBet v 1 trimer: n = 8, and placebo-aluminium hydroxide: n = 9) before the start and after completion of the treatment. PBMC were stimulated with rBet v 1 and analysed for cytokine (IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma)-secreting cells by ELISpot. Bet v 1-specific antibody levels in serum (IgG(1-4), IgE and IgA) were measured by ELISA. Skin prick tests with defined Bet v 1 concentrations were performed before and 10-11 months after the beginning of the study. RESULTS: Bet v 1-specific IgG levels, consisting of IgG(1), IgG(2) and IgG(4), were significantly increased after treatment with recombinant allergen derivatives. Treatment with rBet v 1 trimer led to a significant (p < 0.05) reduction of Bet v 1-reactive IL-5- and IL-13-producing cells, reflecting a reduced Th2 response. In addition, a decreased number of Bet v 1-reactive IL-4 producing (p = 0.07) and an increase of IL-12-producing (p = 0.06) cells was noted in the trimer-treated patients. In contrast to placebo, active treatment resulted in significantly reduced immediate-type skin reactions to Bet v 1 even 10-11 months after treatment. CONCLUSION: Vaccination with recombinant hypoallergenic Bet v 1 derivatives induces a Bet v 1-specific IgG response and leads to reduced skin reactivity in allergic patients. A reduction of Bet v 1-specific Th2 responses was observed in trimer-treated patients, which may reflect the intrinsic property of this allergen derivative. 相似文献