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排序方式: 共有181条查询结果,搜索用时 15 毫秒
91.
Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA) 总被引:2,自引:0,他引:2
Sander JD Dahlborg EJ Goodwin MJ Cade L Zhang F Cifuentes D Curtin SJ Blackburn JS Thibodeau-Beganny S Qi Y Pierick CJ Hoffman E Maeder ML Khayter C Reyon D Dobbs D Langenau DM Stupar RM Giraldez AJ Voytas DF Peterson RT Yeh JR Joung JK 《Nature methods》2011,8(1):67-69
Engineered zinc-finger nucleases (ZFNs) enable targeted genome modification. Here we describe context-dependent assembly (CoDA), a platform for engineering ZFNs using only standard cloning techniques or custom DNA synthesis. Using CoDA-generated ZFNs, we rapidly altered 20 genes in Danio rerio, Arabidopsis thaliana and Glycine max. The simplicity and efficacy of CoDA will enable broad adoption of ZFN technology and make possible large-scale projects focused on multigene pathways or genome-wide alterations. 相似文献
92.
Shaheen FS Znojek P Fisher A Webster M Plummer R Gaughan L Smith GC Leung HY Curtin NJ Robson CN 《PloS one》2011,6(5):e20311
Regardless of the achievable remissions with first line hormone therapy in patients with prostate cancer (CaP), the disease escapes the hormone dependent stage to a more aggressive status where chemotherapy is the only effective treatment and no treatment is curative. This makes it very important to identify new targets that can improve the outcome of treatment. ATM and DNA-PK are the two kinases responsible for signalling and repairing double strand breaks (DSB). Thus, both kinases are pertinent targets in CaP treatment to enhance the activity of the numerous DNA DSB inducing agents used in CaP treatment such as ionizing radiation (IR). Colony formation assay was used to assess the sensitivity of hormone dependent, p53 wt (LNCaP) and hormone independent p53 mutant (PC3) CaP cell lines to the cytotoxic effect of IR and Doxorubicin in the presence or absence of Ku55933 and NU7441 which are small molecule inhibitors of ATM and DNA-PK, respectively. Flow cytometry based methods were used to assess the effect of the two inhibitors on cell cycle, apoptosis and H2AX foci formation. Neutral comet assay was used to assess the induction of DNA DSBs. Ku55933 or NU7441 alone increased the sensitivity of CaP cell lines to the DNA damaging agents, however combining both inhibitors together resulted in further enhancement of sensitivity. The cell cycle profile of both cell lines was altered with increased cell death, DNA DSBs and H2AX foci formation. This study justifies further evaluation of the ATM and DNA-PK inhibitors for clinical application in CaP patients. Additionally, the augmented effect resulting from combining both inhibitors may have a significant implication for the treatment of CaP patients who have a defect in one of the two DSB repair pathways. 相似文献
93.
Curtin ML Frey RR Heyman HR Soni NB Marcotte PA Pease LJ Glaser KB Magoc TJ Tapang P Albert DH Osterling DJ Olson AM Bouska JJ Guan Z Preusser LC Polakowski JS Stewart KD Tse C Davidsen SK Michaelides MR 《Bioorganic & medicinal chemistry letters》2012,22(9):3208-3212
In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations. 相似文献
94.
Aims: The aim of this study was to determine sulphite tolerance for a large number of Dekkera bruxellensis isolates and evaluate the relationship between this phenotype and previously assigned genotype markers. Methods and Results: A published microplate‐based method for evaluation of yeast growth in the presence of sulphite was benchmarked against culturability following sulphite treatment, for the D. bruxellensis type strain (CBS 74) and a reference wine isolate (AWRI 1499). This method was used to estimate maximal sulphite tolerance for 41 D. bruxellensis isolates, which was found to vary over a fivefold range. Significant differences in sulphite tolerance were observed when isolates were grouped according to previously assigned genotypes and ribotypes. Conclusions: Variable sulphite tolerance for the wine spoilage yeast D. bruxellensis can be linked to genotype markers. Significance and Impact of the Study: Strategies to minimize risk of wine spoilage by D. bruxellensis must take into account at least a threefold range in effective sulphite concentration that is dependent upon the genotype group(s) present. The isolates characterized in this study will be a useful resource for establishing the mechanisms conferring sulphite tolerance for this industrially important yeast species. 相似文献
95.
J W Curtin 《Plastic and reconstructive surgery》1989,84(2):340-341
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99.
A novel series of histone deacetylase inhibitors incorporating hetero aromatic ring systems as connection units 总被引:1,自引:0,他引:1
Dai Y Guo Y Curtin ML Li J Pease LJ Guo J Marcotte PA Glaser KB Davidsen SK Michaelides MR 《Bioorganic & medicinal chemistry letters》2003,13(21):3817-3820
A series of structurally novel HDAC inhibitors, in which a hetero aromatic ring connects the spacer with the hydrophobic group, has been designed and synthesized. These new inhibitors are very potent in in vitro enzymatic assays and display antiproliferation activity against two human cancer cell lines. 相似文献
100.
Wada CK Frey RR Ji Z Curtin ML Garland RB Holms JH Li J Pease LJ Guo J Glaser KB Marcotte PA Richardson PL Murphy SS Bouska JJ Tapang P Magoc TJ Albert DH Davidsen SK Michaelides MR 《Bioorganic & medicinal chemistry letters》2003,13(19):3331-3335
Alpha-keto ester and amides were found to be potent inhibitors of histone deacetylase. Nanomolar inhibitors against the isolated enzyme and sub-micromolar inhibitors of cellular proliferation were obtained. The alpha-keto amide 30 also exhibited significant anti-tumor effects in an in vivo tumor model. 相似文献