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81.
Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response 总被引:1,自引:0,他引:1
82.
Virus encoded RNA-silencing suppressors (RSSs) are the key components evolved by the viruses to counter RNA-silencing defense of plants. Whitefly-transmitted begomoviruses infecting tomato crop code for five different proteins, ORF AC4, ORF AC2 and ORF AV2 in DNA-A component, ORF BV1 in DNA-B and ORF βC1 in satellite DNA β which are predicted to function as silencing suppressors. In the present study suppressor function of ORF βC1 of three betasatellites Tomato leaf curl Bangalore betasatellite ToLCBB-[IN:Hess:08], Cotton leaf curl Multan betasatellite CLCuMB–[IN:Sri:02] and Luffa leaf distortion betasatellite LuLDB-[IN:Lu:04] were examined. Agroinfiltration of GFP-silenced Nicotiana tabaccum cv. Xanthi with the cells expressing βC1 protein resulted in reversal of silenced GFP expression. GFP-siRNA level was more than 50-fold lower compared to silenced plants in plants infiltrated with βC1 gene from ToLCBB. However, in the case of 35S-βC1 CLCuMB and 35S-βC1 LuLDB construct, although GFP was expressed, siRNA level was not reduced, indicating that the step at which βC1 interfere in RNA-silencing pathway is different. 相似文献
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Sayle KL Bentley J Boyle FT Calvert AH Cheng Y Curtin NJ Endicott JA Golding BT Hardcastle IR Jewsbury P Mesguiche V Newell DR Noble ME Parsons RJ Pratt DJ Wang LZ Griffin RJ 《Bioorganic & medicinal chemistry letters》2003,13(18):3079-3082
A series of O(4)-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with O(6)-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4'-position were potent inhibitors, with IC(50) values against CDK2 of 1.1+/-0.3 and 34+/-8 nM, respectively. The crystal structure of the 4'-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue. 相似文献
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The vas deferens, seminal vesicle, penis and common genital atrium of the monogenean, Diclidophora merlangi are lined by a very flat, lamellate epithelium. The structure is apparently syncytical, although nuclei or perikaryons have not been observed. The epithelium extends to just inside the gonopore where a septate desmosome marks the union with body tegument. There is minor regional variation in structure. The terminal portion of the seminal vesicle and the penis lumen are lined in part by the luminal cytoplasm of the prostate gland which surrounds this part of the reproductive tract. The prostate gland cells are synthetically active and produce a characteristic secretory body that is released either singly by exocytosis, involving membrane fusion, or in bulk via apocrine secretion. The secretion is acidophilic, PAS-positive and reactive for protein. The penis is sucker-like in structure and armed with a ring of 16 genital hooklets. Cilia have not been observed in any part of the male reproductive tract, and sense receptors are not apparent in the tegument surrounding the gonopore. 相似文献
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Resistance of nicotiana benthamiana to phytophthora infestans is mediated by the recognition of the elicitor protein INF1 总被引:11,自引:0,他引:11 下载免费PDF全文
Phytophthora infestans, the agent of potato and tomato late blight disease, produces a 10-kD extracellular protein, INF1 elicitin. INF1 induces a hypersensitive response in a restricted number of plants, particularly those of the genus Nicotiana. In virulence assays with different P. infestans isolates, five Nicotiana species displayed resistance responses. In all of the interactions, after inoculation with P. infestans zoospores, penetration of an epidermal cell was observed, followed by localized necrosis typical of a hypersensitive response. To determine whether INF1 functions as an avirulence factor in these interactions, we adopted a gene-silencing strategy to inhibit INF1 production. Several transformants deficient in inf1 mRNA and INF1 protein were obtained. These strains remained pathogenic on host plants. However, in contrast to the wild-type and control transformant strains, INF1-deficient strains induced disease lesions when inoculated on N. benthamiana. These results demonstrate that the elicitin INF1 functions as an avirulence factor in the interaction between N. benthamiana and P. infestans. 相似文献
87.
Xin Hui S. Chan Ilsa L. Haeusler Yan Naung Win James Pike Borimas Hanboonkunupakarn Maryam Hanafiah Sue J. Lee Abdoulaye Djimd Caterina I. Fanello Jean-Ren Kiechel Marcus VG Lacerda Bernhards Ogutu Marie A. Onyamboko Andr M. Siqueira Elizabeth A. Ashley Walter RJ Taylor Nicholas J. White 《PLoS medicine》2021,18(9)
BackgroundAmodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.Methods and findingsStudies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression.The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (−1.2 ms, −3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.ConclusionsWhile caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate–reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.In this meta-analysis, Xin Hui Supanee Chan and colleagues investigate the cardiovascular effects of amodiaquine and structurally-related antimalarials using individual patient data from trials. 相似文献
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