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排序方式: 共有243条查询结果,搜索用时 46 毫秒
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The maternal‐zygotic transition and zygotic activation of the Mnemiopsis leidyi genome occurs within the first three cleavage cycles 下载免费PDF全文
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Je-Hyun Yoon Kotb Abdelmohsen Subramanya Srikantan Rong Guo Xiaoling Yang Jennifer L. Martindale Myriam Gorospe 《Nucleic acids research》2014,42(2):1196-1208
In response to stress conditions, many mammalian mRNAs accumulate in stress granules (SGs) together with numerous RNA-binding proteins that control mRNA turnover and translation. However, the signaling cascades that modulate the presence of ribonucleoprotein (RNP) complexes in SGs are poorly understood. Here, we investigated the localization of human antigen R (HuR), an mRNA-stabilizing RNA-binding protein, in SGs following exposure to the stress agent arsenite. Unexpectedly, the mobilization of HuR to SGs was prevented through the activation of Janus kinase 3 (JAK3) by the vitamin K3 analog menadione. JAK3 phosphorylated HuR at tyrosine 200, in turn inhibiting HuR localization in SGs, reducing HuR interaction with targets SIRT1 and VHL mRNAs, and accelerating target mRNA decay. Our findings indicate that HuR is tyrosine-phosphorylated by JAK3, and link this modification to HuR subcytoplasmic localization and to the fate of HuR target mRNAs. 相似文献
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Michael M. Yue Kaosheng Lv Stephen C. Meredith Jennifer L. Martindale Myriam Gorospe Lucia Schuger 《The Journal of biological chemistry》2014,289(49):33971-33983
P311, a conserved 8-kDa intracellular protein expressed in brain, smooth muscle, regenerating tissues, and malignant glioblastomas, represents the first documented stimulator of TGF-β1-3 translation in vitro and in vivo. Here we initiated efforts to define the mechanism underlying P311 function. PONDR® (Predictor Of Naturally Disordered Regions) analysis suggested and CD confirmed that P311 is an intrinsically disordered protein, therefore requiring an interacting partner to acquire tertiary structure and function. Immunoprecipitation coupled with mass spectroscopy identified eIF3 subunit b (eIF3b) as a novel P311 binding partner. Immunohistochemical colocalization, GST pulldown, and surface plasmon resonance studies revealed that P311-eIF3b interaction is direct and has a Kd of 1.26 μm. Binding sites were mapped to the non-canonical RNA recognition motif of eIF3b and a central 11-amino acid-long region of P311, here referred to as eIF3b binding motif. Disruption of P311-eIF3b binding inhibited translation of TGF-β1, 2, and 3, as indicated by luciferase reporter assays, polysome fractionation studies, and Western blot analysis. RNA precipitation assays after UV cross-linking and RNA-protein EMSA demonstrated that P311 binds directly to TGF-β 5′UTRs mRNAs through a previously unidentified RNA recognition motif-like motif. Our results demonstrate that P311 is a novel RNA-binding protein that, by interacting with TGF-βs 5′UTRs and eIF3b, stimulates the translation of TGF-β1, 2, and 3. 相似文献
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Allison B Herman Carlos Anerillas Sophia C Harris Rachel Munk Jennifer
L Martindale Xiaoling Yang Krystyna Mazan-Mamczarz Yongqing Zhang Indra
J Heckenbach Morten Scheibye-Knudsen Supriyo De Payel Sen Kotb Abdelmohsen Myriam Gorospe 《Nucleic acids research》2021,49(13):7389
A major stress response influenced by microRNAs (miRNAs) is senescence, a state of indefinite growth arrest triggered by sublethal cell damage. Here, through bioinformatic analysis and experimental validation, we identified miR-340-5p as a novel miRNA that foments cellular senescence. miR-340-5p was highly abundant in diverse senescence models, and miR-340-5p overexpression in proliferating cells rendered them senescent. Among the target mRNAs, miR-340-5p prominently reduced the levels of LBR mRNA, encoding lamin B receptor (LBR). Loss of LBR by ectopic overexpression of miR-340-5p derepressed heterochromatin in lamina-associated domains, promoting the expression of DNA repetitive elements characteristic of senescence. Importantly, overexpressing miR-340-5p enhanced cellular sensitivity to senolytic compounds, while antagonization of miR-340-5p reduced senescent cell markers and engendered resistance to senolytic-induced cell death. We propose that miR-340-5p can be exploited for removing senescent cells to restore tissue homeostasis and mitigate damage by senescent cells in pathologies of human aging. 相似文献
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The activation of ribulose1, 5-bisphosphate carb-oxylase/oxygenase(Rubisco, EC 4.1.1.39
[EC]
) from the floating angiosperm Spirodelapolyrhiza (L.) Schleid. (giant duckweed) grown at a photon irradianceof 200 or 400 mol photons m2 s1 was consistentlylow, in the range of 5662%. Similarly low values wereobserved with four other emergent aquatic species growing underfull sun irradiance. Transference of Spirodela plants for short(minutes) or long (days) periods to the higher or lower irradianceincreased or decreased, respectively, the activation by onlyabout 15%. Activation was not greatly altered by exposure ofthe plants to full sun irradiance of >2000 mol photons m2s1 or CO2 concentrations in air of 0 and 1170 mol mor1but darkness caused a slow decline to 20% activation. Transientoscillations were observed following a change in irradianceor CO2 concentration indicating that Rubisco was responsiveto environmental perturbations. The low Rubisco activation wasnot due to the tight binding of inhibitors such as carboxyarabinitol-1-phosphate.It is concluded that a substantial proportion of the Rubiscoprotein in these naturally-occurring species may not be usedfor CO2-fixation at any given moment. Key words: Rubisco 相似文献
50.
Amaresh C. Panda Kotb Abdelmohsen Jennifer L. Martindale Clara Di?Germanio Xiaoling Yang Ioannis Grammatikakis Ji Heon Noh Yongqing Zhang Elin Lehrmann Dawood B. Dudekula Supriyo De Kevin G. Becker Elizabeth J. White Gerald M. Wilson Rafael de?Cabo Myriam Gorospe 《Nucleic acids research》2016,44(5):2393-2408