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排序方式: 共有141条查询结果,搜索用时 395 毫秒
81.
Xiang MA Chen RH Demarest KT Gunnet J Look R Hageman W Murray WV Combs DW Patel M 《Bioorganic & medicinal chemistry letters》2004,14(11):2987-2989
A novel series of spirobenzazepines was synthesized and evaluated for V1a and V2 receptor antagonist activity. Compounds 8b, 8i, and 8k have shown selective V1a receptor antagonist activity. Compounds 8p and 8q were shown to be dual V1a/V2 receptor antagonists. 相似文献
82.
Glycosylated dihydrochalcones as potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitors 总被引:2,自引:0,他引:2
Dudash J Zhang X Zeck RE Johnson SG Cox GG Conway BR Rybczynski PJ Demarest KT 《Bioorganic & medicinal chemistry letters》2004,14(20):5121-5125
A series of glucose conjugates was synthesized and tested for inhibition of SGLT1 and SGLT2. The core structure was derived from compound 1a. Modification of the benzofuran moiety and 4'-substituent of the phenyl ring in compound 1a improved selectivity at SGLT2. Select compounds were compared to 1a in metabolic stability and in vivo efficacy studies. 相似文献
83.
Rybczynski PJ Zeck RE Combs DW Turchi I Burris TP Xu JZ Yang M Demarest KT 《Bioorganic & medicinal chemistry letters》2003,13(14):2359-2362
A series of benzoxazinones was synthesized as PPARgamma agonists. The compounds were obtained in seven steps, and SAR was developed by variations to the core shown below. The compounds were tested as functional agonists in the induction of the aP2 gene in preadipocytes, and the most potent compound in the series has an EC(50)=0.51 microM. The potency was further confirmed through a PPAR-Gal4 construct. Efficacy has been demonstrated in the db/db mouse model of hyperglycemia. 相似文献
84.
Matthews JM Chen X Cryan E Hlasta DJ Rybczynski PJ Strauss K Tang Y Xu JZ Yang M Zhou L Demarest KT 《Bioorganic & medicinal chemistry letters》2007,17(24):6773-6778
A series of aminoindane derivatives were synthesized and shown to be potent PPARα agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARα activation and PPARα mediated induction of the HD gene. SAR was developed by variation to the core structure as shown within. Oral bioavailability was demonstrated in a Sprague–Dawley rat, while efficacy to reduce plasma triglycerides and plasma glucose was demonstrated in db/db mice. 相似文献
85.
86.
Eduardo AVF Ramalho Jo?o LQ Silva-Filho Marina FS Cartaxo Carmelita BL Cavalcanti Moacyr JBM Rêgo Maria BM Oliveira Eduardo IC Beltr?o 《Biological research》2014,47(1)
Background
BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.Results
BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.Conclusions
There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis. 相似文献87.
Xiufeng Wu Arlene J Sereno Flora Huang Kai Zhang Micheal Batt Jonathan R Fitchett Dongmei He Heather L Rick Elaine M Conner Stephen J Demarest 《MABS-AUSTIN》2015,7(2):364-376
Immunoglobulins and T cell receptors (TCRs) share common sequences and structures. With the goal of creating novel bispecific antibodies (BsAbs), we generated chimeric molecules, denoted IgG_TCRs, where the Fv regions of several antibodies were fused to the constant domains of the α/β TCR. Replacing CH1 with Cα and CL with Cβ, respectively, was essential for achieving at least partial heavy chain/light chain assembly. Further optimization of the linker regions between the variable and constant domains, as well as replacement of the large FG loop of Cβ with a canonical β-turn, was necessary to consistently obtain full heavy chain/light chain assembly. The optimized IgG_TCR molecules were evaluated biophysically and shown to maintain the binding properties of their parental antibodies. A few BsAbs were generated by co-expressing native Fabs and IgG_TCR Fabs within the same molecular construct. We demonstrate that the IgG_TCR designs steered each of the light chains within the constructs to specifically pair with their cognate heavy chain counterparts. We did find that even with complete constant domain specificity between the CH1/CL and Cα/Cβ domains of the Fabs, strong variable domain interactions can dominate the pairing specificity and induce some mispairing. Overall, the IgG_TCR designs described here are a first step toward the generation of novel BsAbs that may be directed toward the treatment of multi-faceted and complex diseases. 相似文献
88.
AbstractAlthough the New Zealand ground wētā (Anostostomatidae: Hemiandrus) are widespread and abundant, little has been described of their ecology and behaviour. Within the genus several lineages have evolved with ovipositors that are unusually short for this orthopteran family. Some species with this derived morphological character also exhibit maternal care of eggs and offspring. Two new species are described here, Hemiandrus maia sp. nov. and Hemiandrus electra sp. nov. Although morphologically similar with medium length ovipositors, they are not sister taxa and live at opposite ends of South Island, New Zealand. The behaviour of Hemiandrus maia sp. nov. was studied using burrow door re-construction as a key to activity patterns. Observations at night and burrow excavation during the day were used to identify features of their behaviour. Maternal care of both eggs and nymphs was observed. Hemiandrus maia sp. nov. were shown to eat fruit, invertebrates and seeds without discrimination.http://zoobank.org/urn:lsid:zoobank.org:pub:1C7EB0D2-D01B-4D3A-B643-D17813EC2084 相似文献
89.
Thomas A. Rano Ellen Sieber-McMaster Patricia D. Pelton Maria Yang Keith T. Demarest Gee-Hong Kuo 《Bioorganic & medicinal chemistry letters》2009,19(9):2456-2460
Tetrahydroquinoline A is a potent inhibitor of the cholesterol ester transfer protein (CETP), a target for the treatment of low HDL-C and atherosclerosis. Low HDL-C has been identified as a key risk factor for cardiovascular disease in addition to high LDL-C, the target of the statin drugs. Tetrahydroquinoline A inhibits partially purified CETP with an IC50 of 39 nM. The preparation of a series of potent inhibitors of CETP designed around a 1,2,3,4-tetrahydroquinoline platform will be discussed. 相似文献
90.
Davide Sisti Michele Guescini Marco BL Rocchi Pasquale Tibollo Mario D'Atri Vilberto Stocchi 《BMC bioinformatics》2010,11(1):186