全文获取类型
收费全文 | 104篇 |
免费 | 3篇 |
出版年
2021年 | 4篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2015年 | 1篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 8篇 |
2011年 | 11篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 7篇 |
2005年 | 5篇 |
2004年 | 3篇 |
2003年 | 3篇 |
2002年 | 6篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有107条查询结果,搜索用时 15 毫秒
1.
Summary Anoxia has been shown to induce the expression of one or more stress proteins in mammalian cells and tissues. A less severe form of oxygen depletion, hypoxic hypoxia, occurs in response to hypobaric decompression which simulates high altitude conditions. Under these conditions mouse hearts accumulate mRNAs for at least two polypeptides at substantially elevated levels. The molecular weights of these proteins, 85 kDa and 95 kDa, are similar to those reported for other mammalian stress proteins or glucose-regulated proteins. Time course experiments suggest that mRNAs for these species increase continuously for up to 16 hours of treatment, while mRNA for 71 kDa and 79 kDa polypeptides are elevated early in the treatment, but later decrease to control values. Total heart mRNA template activity is also increased by the hypobaric treatment. These results demonstrate that mouse cardiac tissue is capable of mounting a cellular stress-like response when exposed to moderately stressful conditions. It also provides a model for studying the direct effects of acute hypoxic stress on cellular gene expression, and its relationship to physiological adaptation. 相似文献
2.
Georgette Sabeur Gabriel Macaya Farida Kadi Giorgio Bernardi 《Journal of molecular evolution》1993,37(2):93-108
The compositional distributions of high molecular weight DNA fragments from 20 species belonging to 9 out of the 17 eutherian orders were investigated by analytical CsCl density gradient centrifugation and by preparative fractionation in Cs2SO4/BAMD density gradients followed by analysis of the fractions in CsCl. These compositional distributions reflect those of the isochores making up the corresponding genomes. A “general distribution” was found in species belonging to eight mammalian orders. A “myomorph distribution” was found in Myomorpha, but not in the other rodent infraorders Sciuromorpha and Histricomorpha, which share the general distribution. Two other distributions were found in a megachiropteran (but not in microchiropteran, which, again, shares the general distribution) and in pangolin (a species from the only genus of the order Pholidota), respectively. The main difference between the general distribution and all other distributions is that the former contains sizable amounts (6–10%) of GC-rich isochores (detected as DNA fragments equal to, or higher than, 1.710 g/cm3 in modal buoyant density), which are scarce, or absent, in the other distributions. This difference is remarkable because gene concentrations in mammalian genomes are paralleled by GC levels, the highest gene concentrations being present in the GC-richest isochores. The compositional distributions of mammalian genomes reported here shed light on mammalian phylogeny. Indeed, all orders investigated, with the exception of Pholidota, seem to share a common ancestor. The compositional patterns of the megachiropteran and of Myomorpha may be derived from the general pattern or have independent origins. 相似文献
3.
Steven T. Staben Timothy P. Heffron Daniel P. Sutherlin Seema R. Bhat Georgette M. Castanedo Irina S. Chuckowree Jenna Dotson Adrian J. Folkes Lori S. Friedman Leslie Lee John Lesnick Cristina Lewis Jeremy M. Murray Jim Nonomiya Alan G. Olivero Emile Plise Jodie Pang Wei Wei Prior Laurent Salphati Lionel Rouge Bing-Yan Zhu 《Bioorganic & medicinal chemistry letters》2010,20(20):6048-6051
Starting from HTS hit 1a, X-ray co-crystallization and molecular modeling were used to design potent and selective inhibitors of PI3-kinase. Bioavailablity in this series was improved through careful modulation of physicochemical properties. Compound 12 displayed in vivo knockdown of PI3K pharmacodynamic markers such as pAKT, pPRAS40, and pS6RP in a PC3 prostate cancer xenograft model. 相似文献
4.
Vidal A Sabatini M Rolland-Valognes G Renard P Madelmont JC Mounetou E 《Bioorganic & medicinal chemistry》2007,15(6):2368-2374
Among other non-antibiotic properties, tetracyclines inhibit matrix metalloproteinases and are currently under study for the treatment of osteoarthritis. Quaternary ammonium conjugates of tetracyclines were synthesized by direct alkylation of the amine function at the 4-position with methyl iodide. When tested in vitro, they inhibited cytokine-induced MMP expression to a lesser extent than parent tetracyclines. This was compensated by an improved inhibition of MMP catalytic activity. Since inhibition of collagen degradation was maintained these derivatives could be potent drug candidates for cartilage-targeted chondroprotective treatment. 相似文献
5.
6.
Desbois N Gardette M Papon J Labarre P Maisonial A Auzeloux P Lartigue C Bouchon B Debiton E Blache Y Chavignon O Teulade JC Maublant J Madelmont JC Moins N Chezal JM 《Bioorganic & medicinal chemistry》2008,16(16):7671-7690
Various iodo-acridone and acridine carboxamides have been prepared and evaluated as agents for targeted radionuclide and/or chemotherapy for melanoma, due to their structural similarity to benzamides which are known to possess specific affinity for melanin. Three of these carboxamides selected for their in vitro cytotoxic properties were radioiodinated with [(125)I]NaI at high specific activity. Biodistribution studies carried out in B16F0 murine melanoma tumour-bearing mice highlighted that acridone 8f and acridine 9d, presented high, long-lasting tumour concentrations together with an in vivo kinetic profile favourable to application in targeted radionuclide therapy. 相似文献
7.
Kirk D. Robarge Shirley A. Brunton Georgette M. Castanedo Yong Cui Michael S. Dina Richard Goldsmith Stephen E. Gould Oivin Guichert Janet L. Gunzner Jason Halladay Wei Jia Cyrus Khojasteh Michael F.T. Koehler Karen Kotkow Hank La Rebecca L. LaLonde Kevin Lau Leslie Lee Derek Marshall James C. Marsters Minli Xie 《Bioorganic & medicinal chemistry letters》2009,19(19):5576-5581
SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC. 相似文献
8.
Castanedo G Clark K Wang S Tsui V Wong M Nicholas J Wickramasinghe D Marsters JC Sutherlin D 《Bioorganic & medicinal chemistry letters》2006,16(6):1716-1720
The syntheses of potent small molecule inhibitors of the CDK2/cyclinA recruitment site are described. Structure-activity trends of nanomolar octapeptides were examined through amino-acid substitution and truncation of the sequence resulting in the identification of a smaller, albeit significantly less potent, tetrapeptide lead. These losses in affinity were recovered by side-chain optimization and by rigidification of the peptide backbone using a combination of solid-phase parallel synthesis and structure-based design. Finally, two guanidine functionalities were replaced to improve drug-like properties, resulting in neutral small molecules equal in activity to that of the peptide lead. 相似文献
9.
Dollé F Emond P Mavel S Demphel S Hinnen F Mincheva Z Saba W Valette H Chalon S Halldin C Helfenbein J Legaillard J Madelmont JC Deloye JB Bottlaender M Guilloteau D 《Bioorganic & medicinal chemistry》2006,14(4):1115-1125
LBT-999 (8-((E)-4-fluoro-but-2-enyl)-3beta-p-tolyl-8-aza-bicyclo[3.2.1]octane-2beta-carboxylic acid methyl ester), a cocaine derivative belonging to a new generation of highly selective dopamine transporter (DAT) ligands, and its corresponding carboxylic acid derivative, the latter used as precursor for labelling both with tritium and the positron-emitter carbon-11 (half-life: 20.38 min), were synthesized from (R)-cocaine. [(3)H]LBT-999 (>99% radiochemically pure, specific radioactivity of 3.1 TBq/mmol) was prepared from [(3)H]methyl iodide, allowing its in vitro pharmacological evaluation (K(D): 9 nM for DAT and IC(50) > 1000 nM for SERT and NET). Routine production batches of 4.5-9.0 GBq of iv injectable solutions of [(11)C]LBT-999 (with specific radioactivities ranging from 30 to 45 GBq/mumol) were prepared in 25-30 min (HPLC purification and formulation included) using the efficient methylation reagent [(11)C]methyl triflate. The preliminary in vivo pharmacological evaluation of [(11)C]LBT-999, using both biodistributions in rats and brain imaging in monkeys with positron emission tomography (PET), clearly illustrates that this ligand is an excellent candidate for quantification with PET of DAT in humans. 相似文献
10.