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761.
The epithelial sodium channel (ENaC) is regulated by hormones and by other intracellular or extracellular factors. It is activated
by the sulfonylurea drug glibenclamide. The activator effect of glibenclamide is fast and reversible and was observed in Xenopus oocytes coexpressing the α subunit from human, Xenopus, or guinea pig (but not rat) with βγ-rat ENaC subunits. The mechanism of this effect is not yet well understood. We hypothesize
that the extracellular loop of ENaC plays a major role in this activation. Mutants and chimeras of α subunits harboring different
parts of the rat and guinea pig α-subunit extracellular loops were generated and coexpressed with βγ-rat subunits in Xenopus oocytes. The effect of glibenclamide on ENaC activity was measured using two-electrode voltage-clamp technique. The α-rat
ENaC chimera containing the C-terminal part of the extracellular loop of the α-guinea pig ENaC was significantly stimulated
by glibenclamide (1.26-fold), whereas the rat-α combination was not activated by this sulfonylurea. Mutagenesis of specific
residues on the rat α subunit did not generate channels sensitive to glibenclamide, suggesting that the overall structure
of the extracellular loop is required for activation of the channel by this drug. These results support the hypothesis of
the existence of a role played by the last 100 amino acids of the extracellular loop and confirm that the ENaC behaves as
a ligand-gated channel similar to several other members of the ENaC/degenerin family. 相似文献
762.
Susan L. Makris Howard M. Solomon Ruth Clark Kohei Shiota Stephane Barbellion Jochen Buschmann Makoto Ema Michio Fujiwara Konstanze Grote Keith P. Hazelden Kok Wah Hew Masao Horimoto Yojiro Ooshima Meg Parkinson L. David Wise 《Birth defects research. Part B, Developmental and reproductive toxicology》2011,92(6):575-575
763.
Sara Hosseini-Farahabadi Alireza Baradaran-Heravi Carla Zimmerman Kunho Choi Stephane Flibotte Michel Roberge 《PLoS biology》2021,19(5)
Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the extent of PTC readthrough that can be achieved by aminoglycosides like G418. Using a cell-based screen, we identified a small molecule, the phenylpyrazoleanilide Y-320, that potently enhances TP53, DMD, and COL17A1 PTC readthrough by G418. Unexpectedly, Y-320 increased cellular protein levels and protein synthesis, measured by SYPRO Ruby protein staining and puromycin labeling, as well as ribosome biogenesis measured using antibodies to rRNA and ribosomal protein S6. Y-320 did not increase the rate of translation elongation and it exerted its effects independently of mTOR signaling. At the single cell level, exposure to Y-320 and G418 increased ribosome content and protein synthesis which correlated strongly with PTC readthrough. As a single agent, Y-320 did not affect translation fidelity measured using a luciferase reporter gene but it enhanced misincorporation by G418. RNA-seq data showed that Y-320 up-regulated the expression of CXC chemokines CXCL10, CXCL8, CXCL2, CXCL11, CXCL3, CXCL1, and CXCL16. Several of these chemokines exert their cellular effects through the receptor CXCR2 and the CXCR2 antagonist SB225002 reduced cellular protein levels and PTC readthrough in cells exposed to Y-320 and G418. These data show that the self-limiting nature of PTC readthrough by G418 can be compensated by Y-320, a potent enhancer of PTC readthrough that increases ribosome biogenesis and protein synthesis. They also support a model whereby increased PTC readthrough is enabled by increased protein synthesis mediated by an autocrine chemokine signaling pathway. The findings also raise the possibility that inflammatory processes affect cellular propensity to readthrough agents and that immunomodulatory drugs like Y-320 might find application in PTC readthrough therapy.A cell-based screen identifies a small molecule, Y-320, that potently enhances readthrough of premature termination codons by the aminoglycoside G418. Y-320 increases cellular protein levels and protein synthesis, and appears to act via an autocrine chemokine signaling pathway. 相似文献
764.
Carmen Quintana Carmen Lpez-Iglesias Noel Bonnet Stephane Lebonvallet 《Biology of the cell / under the auspices of the European Cell Biology Organization》1993,77(3):307-310
Summary— In a previous paper (Quintana et al, Biol Cell 72, (1991) 167–180) we reported the anti-ovalbumin antibody immunolabeling in the cytoplasm of tubular gland cells from cryofixed, cryosubstituted and acrylic-resin embedded quail oviduct. To confirm these preliminary visual observations, we have carried out a semi-automatic quantitative study of immunogold labeling. The quantitative results confirm the previous data. In addition, we found a significantly higher immunolabeling with low temperature Lowicryl K11M embedding procedure as compared with high temperature LR White embedding. 相似文献
765.
Wei-Fei Chen Yang-Xue Dai Xiao-Lei Duan Na-Nv Liu Wei Shi Na Li Ming Li Shou-Xing Dou Yu-Hui Dong Stephane Rety Xu-Guang Xi 《Nucleic acids research》2016,44(6):2949-2961
Pif1 helicases are ubiquitous members of the SF1B family and are essential for maintaining genome stability. It was speculated that Pif1-specific motifs may fold in specific structures, conferring distinct activities upon it. Here, we report the crystal structures of the Pif1 helicase from Bacteroides spp with and without adenosine triphosphate (ATP) analog/ssDNA. BsPif1 shares structural similarities with RecD2 and Dda helicases but has specific features in the 1B and 2B domains. The highly conserved Pif1 family specific sequence motif interacts with and constraints a putative pin-loop in domain 1B in a precise conformation. More importantly, we found that the 2B domain which contains a specific extended hairpin undergoes a significant rotation and/or movement upon ATP and DNA binding, which is absolutely required for DNA unwinding. We therefore propose a mechanism for DNA unwinding in which the 2B domain plays a predominant role. The fact that the conformational change regulates Pif1 activity may provide insight into the puzzling observation that Pif1 becomes highly processive during break-induced replication in association with Polδ, while the isolated Pif1 has low processivity. 相似文献
766.
Jules Lavalou Qiyan Mao Stefan Harmansa Stephen Kerridge Annemarie C. Lellouch Jean-Marc Philippe Stephane Audebert Luc Camoin Thomas Lecuit 《Developmental cell》2021,56(11):1574-1588.e7
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767.
Stéphanie Torrino Eloise M. Grasset Stephane Audebert Ilyes Belhadj Caroline Lacoux Meagan Haynes Sabrina Pisano Sophie Abélanet Frederic Brau Stephen Y. Chan Bernard Mari William M. Oldham Andrew J. Ewald Thomas Bertero 《Cell metabolism》2021,33(7):1342-1357.e10
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768.
Anne-Christine Macherey Isabelle Leguy Stephane Gregoire Gerard Tainturier Jean-Claude Lhuguenot 《Biology of the cell / under the auspices of the European Cell Biology Organization》1993,77(1):9-11
Summary— Quantitative structure-activity relationship is an effective tool in order to predict drug potency. A similar approach is actually developed for peroxisome proliferation induced by substituted carboxylic acids issued from plasticizer metabolism in rats. The study is focused on acids found in rat urine after adipic diester dosings. Size, location of the substituted group and length of the chain have been studied. 3-D structure has also been taken in account for 2-ethyl hexanoic acids. The results obtained so far demonstrate that peroxisome proliferation potencies of the considered acids are modified according structure changes. At this time location of the group along the chain appears to be a predominant factor. 相似文献
769.
Frédéric Bigey Diego Segond Anne Friedrich Stephane Guezenec Aurélie Bourgais Lucie Huyghe Nicolas Agier Thibault Nidelet Delphine Sicard 《Current biology : CB》2021,31(4):722-732.e5
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770.