全文获取类型
收费全文 | 73篇 |
免费 | 0篇 |
出版年
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 1篇 |
2013年 | 5篇 |
2012年 | 4篇 |
2011年 | 7篇 |
2010年 | 2篇 |
2008年 | 2篇 |
2007年 | 2篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1994年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1933年 | 1篇 |
1930年 | 1篇 |
排序方式: 共有73条查询结果,搜索用时 31 毫秒
1.
Mathivanan Packiarajan Michel Grenon Samuel Zorn Allen T. Hopper Andrew D. White Gamini Chandrasena Xiaosui Pu Robbin M. Brodbeck Albert J. Robichaud 《Bioorganic & medicinal chemistry letters》2013,23(14):4037-4043
A new series of potent fused thiazole mGlu5 receptor positive allosteric modulators (PAMs) (10, 11 and 27–31) are disclosed and details of the SAR and optimization are described. Optimization of alkynyl thiazole 9 (Lu AF11205) led to the identification of potent fused thiazole analogs 10b, 27a, 28j and 31d. In general, substituted cycloalkyl, aryl and heteroaryl carboxamides, and carbamate analogs are mGlu5 PAMs, whereas smaller alkyl carboxamide, sulfonamide and sulfamide analogs tend to be mGlu5 negative allosteric modulators (NAMs). 相似文献
2.
Ahmad S Ngu K Combs DW Wu SC Weinstein DS Liu W Chen BC Chandrasena G Dorso CR Kirby M Atwal KS 《Bioorganic & medicinal chemistry letters》2004,14(1):177-180
Inhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability. 相似文献
3.
Donati I Vetere A Gamini A Skjåk-Braek G Coslovi A Campa C Paoletti S 《Biomacromolecules》2003,4(3):624-631
Coupling of alginate with 1-amino-1-deoxygalactose in the presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide results in a substituted polymer containing galactose side linked via an amide bond. To clarify the degree and pattern of substitution, a (1)H NMR study on the anomeric region of modified alginate, polymannuronate, alginate enriched in guluronic acid (G-enriched alginate), and polyalternating MG, was carried out (G, alpha-l-guluronic acid; M, beta-d-mannuronic acid). From the resonance of the proton at position 1 of galactosylamine, it was possible to determine the amount of galactose linked to mannuronic and to guluronic residues, respectively. Furthermore, (1)H NMR spectroscopy revealed a higher reactivity of guluronic residues for low degrees of conversion. Modified alginates with 7% and 19% of substitution are both able to form stable beads in the presence of calcium ions. The effect of galactose substitution on the dimensions, swelling, and stability of the beads has been studied and the cytotoxicity of the modified polymer evaluated in preliminary biological tests. 相似文献
4.
This study examines mycelial colonization of common soil fungi by bradyrhizobia and an azorhizobial strain, resulting in the
forming of biofilms. The effects of the fungal exudates on a bradyrhizobial strain have also been investigated. Bradyrhizobia
gradually colonized the mycelia for about 18 days, after which the biofilm structures collapsed with the release of the rhizobial
cell clusters to the culture medium. The azorhizobial strain showed differential colonization of the mycelia. In general,
there were no considerable mycotoxin effects of the fungal exudates on the bradyrhizobial strain used, instead the rhizobial
strain utilized the exudates as a source of nutrition. This study indicates that the present microbial association with biofilm
formation has important implications in the survival of rhizobia under adverse soil conditions devoid of vegetation. Further,
it could have developed an as yet unidentified nitrogen fixing system that could have contributed to the nitrogen economy
of soils. 相似文献
5.
Euphorbia pulcherrima Klotz plants exposed to short days (11 h light/13 h dark) for a period of eight weeks, developed flowers and a red canopy consisting of bracts and few true leaves. Plants maintained for three weeks under short day conditions, failed to produce flower primordia or a red canopy in the following 5 weeks in continuous light. Between the 4th and 5th short day week, the youngest leaves began to accumulate anthocyanin and turned red while the apical meristems differentiated into flower primordia. Chlorophyll accumulation ceased at the onset of anthocyanin synthesis and the protein content per unit leaf area declined. mRNA for glutamyl-tRNAGlu synthetase (EC 6.1.1.17) and glutamyl-tRNAGlu reductase also declined during this period. Western blot analysis revealed a loss of glutamyl-tRNAGlu reductase, glutamate 1-semialdehyde (EC 5.4.3.8) and the Mg-chelatase subunits, Olive and CH42, in the last 2 to 4 weeks of the photoperiod. 相似文献
6.
Packiarajan M Marzabadi MR Desai M Lu Y Noble SA Wong WC Jubian V Chandrasena G Wolinsky TD Zhong H Walker MW Wiborg O Andersen K 《Bioorganic & medicinal chemistry letters》2011,21(18):5436-5441
The structure-activity relationship of a series of tricyclic-sulfonamide compounds 11-32 culminating in the discovery of N-[trans-4-(4,5-dihydro-3,6-dithia-1-aza-benzo[e]azulen-2-ylamino)-cyclohexylmethyl]-methanesulfonamide (15, Lu AA33810) is reported. Compound 15 was identified as a selective and high affinity NPY5 antagonist with good oral bioavailability in mice (42%) and rats (92%). Dose dependent inhibition of feeding was observed after i.c.v. injection of the selective NPY5 agonist ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]-hPP). In addition, ip administration of Lu AA33810 (10 mg/kg) produced antidepressant-like effects in a rat model of chronic mild stress. 相似文献
7.
Kastrati I Edirisinghe PD Hemachandra LP Chandrasena ER Choi J Wang YT Bolton JL Thatcher GR 《PloS one》2011,6(11):e27876
There is association between exposure to estrogens and the development and progression of hormone-dependent gynecological cancers. Chemical carcinogenesis by catechol estrogens derived from oxidative metabolism is thought to contribute to breast cancer, yet exact mechanisms remain elusive. Malignant transformation was studied in MCF-10A human mammary epithelial cells, since estrogens are not proliferative in this cell line. The human and equine estrogen components of estrogen replacement therapy (ERT) and their catechol metabolites were studied, along with the influence of co-administration of selective estrogen receptor modulators (SERMs), raloxifene and desmethyl-arzoxifene (DMA), and histone deacetylase inhibitors. Transformation was induced by human estrogens, and selectively by the 4-OH catechol metabolite, and to a lesser extent by an equine estrogen metabolite. The observed estrogen-induced upregulation of CYP450 1B1 in estrogen receptor negative MCF-10A cells, was compatible with a causal role for 4-OH catechol estrogens, as was attenuated transformation by CYP450 inhibitors. Estrogen-induced malignant transformation was blocked by SERMs correlating with a reduction in formation of nucleobase catechol estrogen (NCE) adducts and formation of 8-oxo-dG. NCE adducts can be formed consequent to DNA abasic site formation, but NCE adducts were also observed on incubation of estrogen quinones with free nucleotides. These results suggest that NCE adducts may be a biomarker for cellular electrophilic stress, which together with 8-oxo-dG as a biomarker of oxidative stress correlate with malignant transformation induced by estrogen oxidative metabolites. The observed attenuation of transformation by SERMs correlated with these biomarkers and may also be of clinical significance in breast cancer chemoprevention. 相似文献
8.
Hye-Yeong Kim Johann Sohn Gihani T. Wijewickrama Praneeth Edirisinghe Teshome Gherezghiher Madhubani Hemachandra Pei-Yi Lu R. Esala Chandrasena Mary Ellen Molloy Debra A. Tonetti Gregory R.J. Thatcher 《Bioorganic & medicinal chemistry》2010,18(2):809-821
Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E2) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD–E2 conjugate was explored by cell reporter assays and confocal fluorescence microscopy. In simile with reported dendrimer–E2 conjugates, CD–E2 was found to be a stable, extranuclear receptor selective estrogen that penetrated into the cytoplasm. 相似文献
9.
10.
S I Chandrasena F J Hird 《Comparative biochemistry and physiology. B, Comparative biochemistry》1978,61(2):191-194
1. The content of adenylic acid deaminase and of aspartate-2-oxoglutarate aminotransferase of skeletal muscle tissue from a variety of animals has been determined. 2. White (fast) muscle contained large amounts of adenylic acid deaminase and red (slow) muscle contained large amounts of aspartate aminotransferase. There was a general inverse relationship between the adenylic acid deaminase and the aspartate aminotransferase content of muscles from various vertebrates. Thus, there is no simple correlation between the capacity to produce inosinic acid and ammonia from adenylic acid and the capacity to catalyse the formation of aspartate for conversion of inosinic acid back to adenylic acid. 3. The absence of adenylic acid deaminase from the tail muscles of the yabbie and other invertebrates indicates a marked difference in the Animal Kingdom. 相似文献