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101.
Bloom JD Dushin RG Curran KJ Donahue F Norton EB Terefenko E Jones TR Ross AA Feld B Lang SA DiGrandi MJ 《Bioorganic & medicinal chemistry letters》2004,14(13):3401-3406
A series of highly potent thiourea inhibitors of cytomegalovirus (CMV) with improved stability properties was prepared and evaluated. Compound 29 inhibited the virus in cultured HFF cells with IC50 of 0.2 nM. 相似文献
102.
The secondary intracellular target of human neutrophil peptide-1 has been examined in M. tuberculosis H37Ra. Binding studies with radioiodinated HNP-1 revealed biphasic equilibrium binding kinetics with respect to time. The major
site of HNP-1 binding was found to be plasma membrane/cell wall whereas the cytosol appears to be a secondary site. Among
the different macromolecules examined, maximum inhibition (75%) was observed in DNA biosynthesis during treatment with HNP-1.
The interaction of HNP-1 with mycobacterial genomic DNA on the basis of gel retardation assay revealed HNP-1 binding to DNA.
These results indicate that HNP-1 has DNA as the secondary intracellular target for antibacterial action against mycobacteria.
Received: 25 October 2000/Accepted: 10 January 2001 相似文献
103.
Diaz JE Lin CS Kunishiro K Feld BK Avrantinis SK Bronson J Greaves J Saven JG Weiss GA 《Protein science : a publication of the Protein Society》2011,20(9):1597-1606
Terpenoids include structurally diverse antibiotics, flavorings, and fragrances. Engineering terpene synthases for control over the synthesis of such compounds represents a long sought goal. We report computational design, selections, and assays of a thermostable mutant of tobacco 5-epi-aristolochene synthase (TEAS) for the catalysis of carbocation cyclization reactions at elevated temperatures. Selection for thermostability included proteolytic digestion followed by capture of intact proteins. Unlike the wild-type enzyme, the mutant TEAS retains enzymatic activity at 65°C. The thermostable terpene synthase variant denatures above 80°C, approximately twice the temperature of the wild-type enzyme. 相似文献
104.
Veronica Dahm Daniel Hering Dirk Nemitz Wolfram Graf Astrid Schmidt-Kloiber Patrick Leitner Andreas Melcher Christian K. Feld 《Hydrobiologia》2013,704(1):389-415
The majority of studies comparing the response of biotic metrics to environmental stress in rivers are based on relatively small, homogeneous datasets resulting from research projects. Here, we used a large dataset from Austrian and German national river monitoring programmes (2,302 sites) to analyse the response of fish, diatom and macroinvertebrate metrics to four stressors acting at different scales (hydromorphology, physico-chemistry, riparian and catchment land use). Nutrient enrichment and catchment land use were the main discriminating stressors for all organism groups, over-ruling the effects of hydromorphological stress on the site scale. The response of fish metrics to stress was generally low, while macroinvertebrate metrics performed best. The Trophic Diatom Index (TDI) responded most strongly to all stressors in the mountain streams, while different metrics were responsive in the lowlands. Our results suggest that many rivers are still considerably affected by nutrient enrichment (eutrophication), which might directly point at implications of catchment land use. We conclude that monitoring datasets are well-suited to detect major broad-scale trends of degradation and their impact on riverine assemblages, while the more subtle effects of local-scale stressors require stream type-specific approaches. 相似文献
105.
Identification of small molecule compounds that selectively inhibit varicella-zoster virus replication 下载免费PDF全文
Visalli RJ Fairhurst J Srinivas S Hu W Feld B DiGrandi M Curran K Ross A Bloom JD van Zeijl M Jones TR O'Connell J Cohen JI 《Journal of virology》2003,77(4):2349-2358
A series of nonnucleoside, N-alpha-methylbenzyl-N'-arylthiourea analogs were identified which demonstrated selective activity against varicella-zoster virus (VZV) but were inactive against other human herpesviruses, including herpes simplex virus. Representative compounds had potent activity against VZV early-passage clinical isolates and an acyclovir-resistant isolate. Resistant viruses generated against one inhibitor were also resistant to other compounds in the series, suggesting that this group of related small molecules was acting on the same virus-specific target. Sequencing of the VZV ORF54 gene from two independently derived resistant viruses revealed mutations in ORF54 compared to the parental VZV strain Ellen sequence. Recombinant VZV in which the wild-type ORF54 sequence was replaced with the ORF54 gene from either of the resistant viruses became resistant to the series of inhibitor compounds. Treatment of VZV-infected cells with the inhibitor impaired morphogenesis of capsids. Inhibitor-treated cells lacked DNA-containing dense-core capsids in the nucleus, and only incomplete virions were present on the cell surface. These data suggest that the VZV-specific thiourea inhibitor series block virus replication by interfering with the function of the ORF54 protein and/or other proteins that interact with the ORF54 protein. 相似文献
106.
Ilan Ben-Zvi Tami Krichely-Vachdi Olga Feld Merav Lidar Shaye Kivity Avi Livneh 《Orphanet journal of rare diseases》2014,9(1):1-6
Background
To demonstrate and clinically, genetically and demographically characterize familial Mediterranean fever (FMF) patients, maintaining remission despite colchicine abstinence.Methods
FMF patients were screened for an endurance of prolonged remission (≥ 3 years), despite refraining from colchicine. Clinical, demographic and genetic parameters were collected. Data were compared with those of consecutive control FMF subjects, coming to the clinic for their periodic follow up examination.Results
Of 1000 patients screened over 5 years, 33 manifested colchicine-free remission. The mean duration of the remission period was 12.6?±?8.1 years. Patients in the remission group had milder severity of FMF, compared to the control group (22 vs. 11 patients with mild disease, respectively, p?=?0.003) and a longer diagnosis delay (21?±?15.7 vs. 13.4?±?13.5 years, respectively, p?=?0.04). Patients experiencing remission suffered mostly of abdominal attacks, low rate of attacks in other sites and low rate of chronic and non-attack manifestations. When the disease resumed activity, it responded well to colchicine, despite using a lower dose, as compared to the control subjects (p?<?0.001). None of the patients in this group was homozygous for the M694V mutation (p?=?0.0008).Conclusions
Prolonged colchicine-free remission defines a rare and milder form of FMF with unique clinical, demographic, and molecular characteristics. 相似文献107.
I. Novel HCV NS5B polymerase inhibitors: discovery of indole 2-carboxylic acids with C3-heterocycles
Anilkumar GN Lesburg CA Selyutin O Rosenblum SB Zeng Q Jiang Y Chan TY Pu H Vaccaro H Wang L Bennett F Chen KX Duca J Gavalas S Huang Y Pinto P Sannigrahi M Velazquez F Venkatraman S Vibulbhan B Agrawal S Butkiewicz N Feld B Ferrari E He Z Jiang CK Palermo RE McMonagle P Huang HC Shih NY Njoroge G Kozlowski JA 《Bioorganic & medicinal chemistry letters》2011,21(18):5336-5341
SAR development of indole-based palm site inhibitors of HCV NS5B polymerase exemplified by initial indole lead 1 (NS5B IC(50)=0.9 μM, replicon EC(50)>100 μM) is described. Structure-based drug design led to the incorporation of novel heterocyclic moieties at the indole C3-position which formed a bidentate interaction with the protein backbone. SAR development resulted in leads 7q (NS5B IC(50)=0.032 μM, replicon EC(50)=1.4 μM) and 7r (NS5B IC(50)=0.017 μM, replicon EC(50)=0.3 μM) with improved enzyme and replicon activity. 相似文献
108.
R S Gurjar V Backman L T Perelman I Georgakoudi K Badizadegan I Itzkan R R Dasari M S Feld 《Nature medicine》2001,7(11):1245-1248
Biomedical imaging with light-scattering spectroscopy (LSS) is a novel optical technology developed to probe the structure of living epithelial cells in situ without need for tissue removal. LSS makes it possible to distinguish between single backscattering from epithelial-cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative information about the epithelial-cell nuclei such as nuclear size, degree of pleomorphism, degree of hyperchromasia and amount of chromatin. LSS imaging allows mapping these histological properties over wide areas of epithelial lining. Because nuclear enlargement, pleomorphism and hyperchromasia are principal features of nuclear atypia associated with precancerous and cancerous changes in virtually all epithelia, LSS imaging can be used to detect precancerous lesions in optically accessible organs. 相似文献
109.
Douglas Darden Michael Eskander Gregory K. Feld 《Indian pacing and electrophysiology journal》2021,21(3):191-195
A 51-year-old male developed recurrent episodes of palpitations and pre-syncope after surgical aortic valve replacement. Electrocardiograms after surgery revealed a wide complex tachycardia with alternating left bundle branch and right bundle branch block morphologies. An electrophysiology study (EPS) demonstrated typical bundle branch reentry ventricular tachycardia (BBRVT) treated successfully with right bundle ablation. We demonstrate the key diagnostic features of BBRVT on EPS, describe the circuit of BBRVT with explanation of the HV pseudointerval, and highlight the association of BBRVT and valve replacement. 相似文献
110.
To evaluate breastfed infants' responses to scented objects, we videotaped
the facial and bodily reactions of sixty-three infants as they explored, in
succession, three toys that were identical in appearance but different in
their characteristic odor. Two of the toys were scented with odorants
previously shown to be transmitted to human milk, one with ethanol and the
other with vanilla, whereas the third toy was unscented. Each videotape was
subjected to frame-by-frame analysis to measure a variety of behaviors that
are considered either to be exploratory in nature in that they lead to
perceptual information about the object or to reflect the infants' hedonic
reaction. Analyses of these behaviors revealed that the infants looked more
and vocalized less in the presence of the vanilla-scented toy and spent
less time manipulating the ethanol-scented toy when compared with the
unscented toy. Moreover, differential exposure to the odors of ethanol and
vanilla, as indicated by differential consumption of alcohol by a parent or
use of vanilla-scented product by the mother, was related to differential
responses to these odors. These findings suggest that human infants are
able to detect and retain information about the chemical features of their
environment.
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