全文获取类型
收费全文 | 123篇 |
免费 | 20篇 |
专业分类
妇产科学 | 1篇 |
基础医学 | 22篇 |
口腔科学 | 9篇 |
临床医学 | 15篇 |
内科学 | 22篇 |
皮肤病学 | 29篇 |
神经病学 | 1篇 |
预防医学 | 1篇 |
眼科学 | 1篇 |
药学 | 35篇 |
肿瘤学 | 7篇 |
出版年
2022年 | 1篇 |
2019年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 1篇 |
2013年 | 4篇 |
2012年 | 4篇 |
2011年 | 6篇 |
2010年 | 4篇 |
2009年 | 3篇 |
2008年 | 3篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 1篇 |
2004年 | 4篇 |
2003年 | 1篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 12篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 13篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有143条查询结果,搜索用时 15 毫秒
21.
Revankar SG 《Seminars in respiratory and critical care medicine》2004,25(2):183-189
Dematiaceous fungi are the etiologic agents of phaeohyphomycosis and are increasingly recognized as causing disease in humans. A wide variety of infectious syndromes are seen, from local infections due to trauma to widely disseminated infection in immunocompromised patients. Pulmonary disease may be divided into allergic bronchopulmonary and nonallergic syndromes, depending on the species. These fungi have unique pathogenic mechanisms owing to the presence of melanin in their cell walls, which imparts the characteristic dark color to their spores and hyphae. Melanin is a known virulence factor in certain fungi, including Cryptococcus neoformans and Wangiella dermatitidis. Therapy depends upon the clinical syndrome. Local infection may be cured with excision alone, whereas systemic disease is often refractory to therapy. Azoles such as itraconazole and voriconazole have the most consistent in vitro activity, though there is more clinical experience with itraconazole. Further studies are needed to better understand the pathogenesis and treatment of these uncommon infections. 相似文献
22.
K Ramasamy B G Ugarkar P A McKernan R K Robins G R Revankar 《Journal of medicinal chemistry》1986,29(11):2231-2235
Several 3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazines related to formycin were prepared and tested for their antitumor activity in cell culture. Dehydrative coupling of 3-amino-6-hydrazino-1,2,4-triazin-5(4H)-one (5) with 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonic acid (6a) and further ring closure of the reaction product (7) provided 6-amino-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,2,4-triazolo[3,4- f]-1,2,4-triazin-8(7H)-one (8). Condensation of 5 with 3,4,6-tri-O-benzoyl-2,5-anhydro-D-allonic acid chloride (6b), followed by ring annulation, also gave 8 in good yield. Debenzoylation of 8 furnished the guanosine analogue 6-amino-3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazin -8(7H)-one (4b). Thiation of 8 with P2S5, followed by debenzoylation of the thiated product (11a), afforded 6-amino-3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazin -8(7H)- thione (11b). Methylation of the sodium salt of 11a gave the 8-methylthio derivative (10), which on ammonolysis furnished 6,8-diamino-3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4-f]-1,2,4-triazine (9). Diazotization of 10 with tert-butyl nitrite (TBN) and SbCl3 in 1,2-dichloroethane gave the corresponding 6-chloro derivative (12a). Reaction of 10 with TBN in THF in the absence of a halogen source gave 8-(methylthio)-3-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-1,2,4- triazolo[3,4-f]-1,2,4-triazine (12b). Ammonolysis of 12b gave the azaformycin A analogue 8-amino-3-beta-D-ribofuranosyl-1,2,4- triazolo[3,4-f]-1,2,4-triazine (3), which on deamination afforded 3-beta-D-ribofuranosyl-1,2,4-triazolo[3,4- f]-1,2,4-triazin-8(7H)-one (4a). The azaformycin A analogue (3) showed pronounced inhibitory effects against L1210, WIL2, and CCRF-CEM cell lines with ID50 values ranging from 5.0 to 7.3 microM. 相似文献
23.
Donald F. Smee Patricia A. McKernan Hassan A. Alaghamandan Karl B. Frank Kandasamy Ramasamy Ganapathi R. Revankar Roland K. Robins 《Antiviral research》1988,10(6):263-277
Eight sugar-modified pyrrolopyrimidine nucleoside analogs related to the antibiotic sangivamycin were evaluated in cell culture against herpes simplex types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), adenovirus, and visna virus. Five of the compounds were highly active against most of the viruses with 50% inhibition (ED50) values of 1–10 μM. The selectivity of the agents was low, with inhibition of uninfected cell proliferation occurring within 5-fold that of the virus ED50 for most of the viruses. The compounds did not possess RNA virus-inhibitory activity when evaluated against certain myxo-, paramyxo-, picorna-, reo-, rhabdo-, and togaviruses. Two of the nucleosides were tested further in a cell line persistently infected with Friend leukemia virus where they were inhibitory to both virus yield and cell proliferation at 4–5 μM. Several of the sangivamycin analogs were tested in animal models using a twice-a-day treatment regimen. They proved to be inactive against HSV-1, murine CMV and/or Friend leukemia virus infections in mice. 相似文献
24.
Y S Sanghvi N B Hanna S B Larson J M Fujitaki R C Willis R A Smith R K Robins G R Revankar 《Journal of medicinal chemistry》1988,31(2):330-335
The 5-amino and certain related derivatives of the powerful purine nucleoside phosphorylase (PNPase) inhibitor 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine (TCNR,3) have been prepared and evaluated for their PNPase activity. Acetylation followed by dehydration of 5-chloro-1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (4a) gave 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1,2,4-triazole-3- carbonitrile (5). Ammonolysis of 5 furnished 5-amino-1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine (5-amino-TCNR, 6), the structure of which was assigned by single-crystal X-ray analysis. Acid-catalyzed fusion of methyl 5-chloro-1,2,4-triazole-3-carboxylate (7a) with 5-deoxy-1,2,3-tri-O-acetyl-D-ribofuranose (8) gave methyl 5-chloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)- 1,2,4-triazole-3-carboxylate (9a) and the corresponding positional isomer 9b. Transformation of the functional groups in 9a afforded a route to 5'-deoxyribavirin (9i). Compound 9a was converted in four steps to 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3- carboxamidine (5'-deoxy-5-amino-TCNR, 9g). Similar acid-catalyzed fusion of 1,2,4-triazole-3-carbonitrile (7b) with 8 and ammonolysis of the reaction product 9h gave yet another route to 9i. Treatment of 9h with NH3/NH4Cl furnished 1-(5-deoxy-beta-D-ribofuranosyl)- 1,2,4-triazole-3-carboxamidine (5'-deoxy-TCNR, 9k). The C-nucleoside congener of TCNR (3-beta-D-ribofuranosyl- 1,2,4-triazole-5-carboxamidine, 12) was prepared in two steps from 3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)- 1,2,4-triazole-5-carbonitrile (10) by conventional procedure. 5-Amino-TCNR (6) displayed a more potent, high-affinity inhibition than TCNR, with a Ki of 10 microM. In contrast, 5'-deoxy-5-amino-TCNR (9g) was a significantly less potent inhibitor of PNPase, compared to 5'-deoxy-TCNR (Ki = 80 and 20 microM, respectively). Neither the C-nucleoside congener of TCNR (12) nor that of ribavirin were found to inhibit inosine phosphorolysis. 相似文献
25.
26.
C R Petrie H B Cottam P A McKernan R K Robins G R Revankar 《Journal of medicinal chemistry》1985,28(8):1010-1016
Several 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides were prepared and tested for their biological activity. High-temperature glycosylation of 3,6-dibromoallopurinol with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of BF3 X OEt2, followed by ammonolysis, provided 6-amino-3-bromo-1-beta-D-ribofuranosylpyrazolo-[3,4-d]pyrimidin-4(5H)-on e. Similar glycosylation of either 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl sulfoxide or 6-amino-3-bromopyrazolo [3,4-d]pyrimidin-4(5H)-one, and subsequent ammonolysis, also gave 7a. The structural assignment of 7a was on the basis of spectral studies, as well as its conversion to the reported guanosine analogue 1d. Application of this glycosylation procedure to 6-(methylthio)-4(5H)-oxopyrazolo[3,4-d]pyrimidine-3-carboxamide gave the corresponding N-1 glycosyl derivative. Dethiation and debenzoylation of 16a provided an alternate route to the recently reported 3-carbamoylallopurinol ribonucleoside thus confirming the structural assignment of 16a and the nucleosides derived therefrom. Oxidation of 16a and subsequent ammonolysis afforded 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carboxamide. Alkaline treatment of 15a gave 6-azacadeguomycin. Acetylation of 15a, followed by dehydration with phosgene, provided the versatile intermediate 6-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4(5H)-oxopyrazolo [3, 4-d]pyrimidine-3-carbonitrile. Deacetylation of 19 gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carbonitrile. Reaction of 19 with H2S gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-thiocarboxamide. All of these compounds were tested in vitro against certain viruses and tumor cells. Among these compounds, the guanosine analogues 7a and 20a showed significant activity against measles in vitro and were found to exhibit moderate antitumor activity in vitro against L1210 and P388 leukemia. 6-Azacadeguomycin and all other compounds were inactive against the viruses and tumor cells tested in vitro. 相似文献
27.
S H Kim D G Bartholomew L B Allen R K Robins G R Revankar 《Journal of medicinal chemistry》1978,21(9):883-889
The first chemical synthesis of 2-aminoimidazo[1,2-a]-s-triazin-4-one (8), the corresponding nucleoside and nucleotide, and certain related derivatives of a new class of purine analogues containing a bridgehead nitrogen atom is described. Condensation of 2-amino-4-chloro-6-hydroxy-s-triazine (2) with aminoacetaldehyde dimethyl acetal followed by the ring annulation gave the guanine analogue 8. A similar ring annulation of 4-(2,2-dimethoxyethylamino)-s-triazine-2,6-dione (5) gave imidazo[1,2-a]-s-triazine-4,6-dione (9). Direct glycosylation of the trimethylsilyl derivative of 8 with 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose in the presence of stannic chloride, followed by debenzoylation, gave the guanosine analogue 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one (12b), which on deamination gave the xanthosine analogue 13. Phosphorylation of 12b gave 2-amino-8-(beta-D-ribofuranosyl)imidazo[1,2-a]-s-triazin-4-one 5'-monophosphate (II). The anomeric configuration has been determined unequivocally by using NMR of the 2',3'-O-isopropylidene derivate 10 and the site of ribosylation has been established by using 13C NMR spectroscopy. These compounds were tested against type 1 herpes, type 13 rhino, and type 3 parainfluenza viruses in tissue culture. Moderate rhinovirus activity was observed for several compounds at nontoxic dosage levels. 相似文献
28.
Synthesis and biological activity of 5-thiobredinin and certain related 5-substituted imidazole-4-carboxamide ribonucleosides 总被引:1,自引:0,他引:1
S G Wood K G Upadhya N K Dalley P A McKernan P G Canonico R K Robins G R Revankar 《Journal of medicinal chemistry》1985,28(9):1198-1203
A number of 5-substituted imidazole-4-carboxamide ribonucleosides were prepared and tested for their biological activity. Treatment of 5-chloro-1-beta-D-ribofuranosylimidazole-4-carboxamide (2) with methanethiol provided 5-(methylthio)-1-beta-D-ribofuranosylimidazole-4-carboxamide (3a). Similar treatment of 2 with ethanethiol or benzenemethanethiol gave the corresponding 5-ethylthio and 5-benzylthio derivatives 3b and 3c. Oxidation of 3a and 3b with m-chloroperoxybenzoic acid furnished the corresponding sulfonyl derivatives 4a and 4b. Reductive cleavage of 3c with sodium naphthalene or Na/NH3 gave 5-mercapto-1-beta-D-ribofuranosylimidazole-4-carboxamide (5-thiobredinin, 5). Direct treatment of 2 with sodium hydrosulfide provided an alternate route to 5, the structure of which was established by single-crystal X-ray analysis. 5-Thiobredinin has a zwitterionic structure similar to that of bredinin. Glycosylation of persilylated ethyl 5(4)-methylimidazole-4(5)-carboxylate (6) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of SnCl4 provided a quantitative yield of the corresponding tri-O-benzoyl nucleoside 7. Debenzoylation of 7 with MeOH/NH3 at ambient temperature gave ethyl 5-methyl-1-beta-D-ribofuranosylimidazole-4-carboxylate (8). Further ammonolysis of 8 or 7 at elevated temperature and pressure gave 5-methyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (9). All of these ribonucleosides were tested in Vero cell cultures and in mice against certain viruses. Compounds 3a and 3c exhibited significant activity against vaccinia virus in vitro, whereas 4a was effective against Rift Valley fever virus in mice. 5-Thiobredinin failed to exhibit appreciable antiviral or cytostatic activity (against L1210 and P388) in cell culture. 相似文献
29.
30.