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排序方式: 共有81条查询结果,搜索用时 31 毫秒
1.
W D George E N Gleave P C England M C Wilson R A Sellwood D Asbury G Hartley P G Barker P Hobbs J Wakefield 《BMJ (Clinical research ed.)》1976,2(6040):832-833
The feasibility of mass population screening for breast cancer by clinical examination and x-ray mammography was studied. The results indicate that such a programme could be conducted effectively by non-medical staff and be safe from the dangers of irradiation. The response rate of women invited for screening suggests that such a service is acceptable to the general public. The additional work load produced by screening would not overburden the existing surgical services. 相似文献
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Syam Prakash Somasekharan Neetu Saxena Fan Zhang Eliana Beraldi Jia
Ni Huang Christina Gentle Ladan Fazli Marisa Thi Poul
H Sorensen Martin Gleave 《Nucleic acids research》2022,50(2):1069
We report a new mechanism of androgen receptor (AR) mRNA regulation and cytoprotection in response to AR pathway inhibition (ARPI) stress in prostate cancer (PCA). AR mRNA translation is coordinately regulated by RNA binding proteins, YTHDF3 and G3BP1. Under ambient conditions m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. When AR-regulated PCA cell lines are subjected to ARPI stress, m6A-modified AR mRNA is recruited from actively translating polysomes (PSs) to RNA-protein stress granules (SGs), leading to reduced AR mRNA translation. After ARPI stress, m6A-modified AR mRNA liquid–liquid phase separated with YTHDF3, while m6A-unmodified AR mRNA phase separated with G3BP1. Accordingly, these AR mRNA messages form two distinct YTHDF3-enriched or G3BP1-enriched clusters in SGs. ARPI-induced SG formation is cell-protective, which when blocked by YTHDF3 or G3BP1 silencing increases PCA cell death in response to ARPI stress. Interestingly, AR mRNA silencing also delays ARPI stress-induced SG formation, highlighting its supportive role in triggering this stress response. Our results define a new mechanism for stress adaptive cell survival after ARPI stress involving SG-regulated translation of AR mRNA, mediated by m6A RNA modification and their respective regulatory proteins. 相似文献
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P. D. Needham R. G. Atkinson B. A. M. Morris R. C. Gardner A. P. Gleave 《Plant cell reports》1998,17(8):631-639
We have constructed a binary vector containing elements of the monopartite geminivirus, tobacco yellow dwarf virus (TYDV).
The vector is designed to be stably integrated into the plant genome, via Agrobacterium-mediated transfer. Upon expression of the viral replication-associated protein the TYDV elements are released from the T-DNA
and then replicate episomally. We refer to these released forms as multicopy plant episomes (MPE). Tobacco plants (Nicotiana tabacum cv `Samsun') transformed with the vector showed MPE release and subsequent episomal replication in 6 of 11 of these plants.
An MPE vector containing the uidA gene faithfully replicated and maintained the reporter gene, even though the construct was considerably larger than the wild-type
TYDV genome. Histochemical staining revealed a speckled GUS expression phenotype which could be correlated with MPE replication.
Received: 11 July 1997 / Revision received: 4 November 1997 / Accepted: 8 December 1997 相似文献
5.
Robert J. Gleave Daryl S. Walter Paul J. Beswick Elena Fonfria Anton D. Michel Shilina A. Roman Sac-Pham Tang 《Bioorganic & medicinal chemistry letters》2010,20(16):4951-4954
A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure–activity relationships (SAR) were investigated both with respect to activity at the P2X7 receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X7 antagonist with reduced in vitro metabolism and high solubility. 相似文献
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Mugabe C Matsui Y So AI Gleave ME Heller M Zeisser-Labouèbe M Heller L Chafeeva I Brooks DE Burt HM 《Biomacromolecules》2011,12(4):949-960
The objective of this study was to evaluate the tolerability, to establish a dosing regimen, and to evaluate the efficacy of intravesical docetaxel (DTX) formulations in a mouse model of bladder cancer. DTX in commercial formulation (Taxotere, DTX in Tween 80) or loaded in hyperbranched polyglycerols (HPGs) was evaluated. The synthesis and characterization of HPGs with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) in the shell and further functionalized with amine groups (HPG-C(8/10)-MePEG and HPG-C(8/10)-MePEG-NH(2)) is described. Intravesical DTX in either commercial or HPGs formulations (up to 1.0 mg/mL) was instilled in mice with orthotopic bladder cancer xenografts and was well tolerated with no apparent signs of local or systemic toxicities. Furthermore, a single dose of intravesical DTX (0.5 mg/mL) loaded in HPGs was significantly more effective in reducing the tumor growth in an orthotopic model of bladder cancer than the commercial formulation of Taxotere. In addition, DTX-loaded HPG-C(8/10)-MePEG-NH(2) was found to be more effective at lower instillation dose than DTX (0.2 mg/mL)-loaded HPG-C(8/10)-MePEG. Overall, our data show promising antitumor efficacy and safety in a recently validated orthotopic model of bladder cancer. Further research is warranted to evaluate its safety and efficacy in early phase clinical trials in patients refractory to standard intravesical therapy. 相似文献
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Beswick P Charrier N Clarke B Demont E Dingwall C Dunsdon R Faller A Gleave R Hawkins J Hussain I Johnson CN MacPherson D Maile G Matico R Milner P Mosley J Naylor A O'Brien A Redshaw S Riddell D Rowland P Skidmore J Soleil V Smith KJ Stanway S Stemp G Stuart A Sweitzer S Theobald P Vesey D Walter DS Ward J Wayne G 《Bioorganic & medicinal chemistry letters》2008,18(3):1022-1026
This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays. 相似文献
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Alexander W Wyatt Fan Mo Kendric Wang Brian McConeghy Sonal Brahmbhatt Lina Jong Devon M Mitchell Rebecca L Johnston Anne Haegert Estelle Li Janet Liew Jake Yeung Raunak Shrestha Anna V Lapuk Andrew McPherson Robert Shukin Robert H Bell Shawn Anderson Jennifer Bishop Antonio Hurtado-Coll Hong Xiao Arul M Chinnaiyan Rohit Mehra Dong Lin Yuzhuo Wang Ladan Fazli Martin E Gleave Stanislav V Volik Colin C Collins 《Genome biology》2014,15(8)