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81.
Hepatitis C virus (HCV) translation is mediated by an internal ribosome entry site (IRES) located at the 5′ end of the genomic
RNA. The 3′ untranslatable region (3′UTR) stimulates translation by the recruitment of protein factors that simultaneously
bind to the 5′ end of the viral genome. This leads to the formation of a macromolecular complex with a closed loop conformation,
similar to that described for the cap-translated mRNAs. We previously demonstrated the existence of a long-range RNA–RNA interaction
involving subdomain IIId of the IRES region and the stem–loop 5BSL3.2 of the CRE element at the 3′ end of the viral genome.
The present study provides evidence that the enhancement of HCV IRES-dependent translation mediated by the 3′UTR is negatively
controlled by the CRE region in the human hepatoma cell lines Huh-7 and Hep-G2 in a time-dependent manner. Domain 5BSL3.2
is the major partner in this process. Mutations in this motif lead to an increase in IRES activity by up to eightfold. These
data support the existence of a functional high order structure in the HCV genome that involves two evolutionarily conserved
RNA elements, domain IIId in the IRES and stem–loop 5BSL3.2 in the CRE region. This interaction could have a role in the circularisation
of the viral genome. 相似文献
82.
Cristina Lanni Stefano Govoni Adele Lucchelli Cinzia Boselli 《Cellular and molecular life sciences : CMLS》2009,66(18):2985-3008
Clinical depression is viewed as a physical and psychic disease process having a neuropathological basis, although a clear
understanding of its ethiopathology is still missing. The observation that depressive symptoms are influenced by pharmacological
manipulation of monoamines led to the hypothesis that depression results from reduced availability or functional deficiency
of monoaminergic transmitters in some cerebral regions. However, there are limitations to current monoamine theories related
to mood disorders. Recently, a growing body of experimental data has showed that other classes of endogenous compounds, such
as neuropeptides and amino acids, may play a significant role in the pathophysiology of affective disorders. With the development
of neuroscience, neuronal networks and intracellular pathways have been identified and characterized, describing the existence
of the interaction between monoamines and receptors in turn able to modulate the expression of intracellular proteins and
neurotrophic factors, suggesting that depression/antidepressants may be intermingled with neurogenesis/neurodegenerative processes. 相似文献
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Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
87.
Stacey SN Sulem P Jonasdottir A Masson G Gudmundsson J Gudbjartsson DF Magnusson OT Gudjonsson SA Sigurgeirsson B Thorisdottir K Ragnarsson R Benediktsdottir KR Nexø BA Tjønneland A Overvad K Rudnai P Gurzau E Koppova K Hemminki K Corredera C Fuentelsaz V Grasa P Navarrete S Fuertes F García-Prats MD Sanambrosio E Panadero A De Juan A Garcia A Rivera F Planelles D Soriano V Requena C Aben KK van Rossum MM Cremers RG van Oort IM van Spronsen DJ Schalken JA Peters WH Helfand BT Donovan JL 《Nature genetics》2011,43(11):1098-1103
To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27). 相似文献
88.
Hashibe M McKay JD Curado MP Oliveira JC Koifman S Koifman R Zaridze D Shangina O Wünsch-Filho V Eluf-Neto J Levi JE Matos E Lagiou P Lagiou A Benhamou S Bouchardy C Szeszenia-Dabrowska N Menezes A Dall'Agnol MM Merletti F Richiardi L Fernandez L Lence J Talamini R Barzan L Mates D Mates IN Kjaerheim K Macfarlane GJ Macfarlane TV Simonato L Canova C Holcátová I Agudo A Castellsagué X Lowry R Janout V Kollarova H Conway DI McKinney PA Znaor A Fabianova E Bencko V Lissowska J Chabrier A Hung RJ 《Nature genetics》2008,40(6):707-709
Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology. 相似文献
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