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141.
Angell RM Atkinson FL Brown MJ Chuang TT Christopher JA Cichy-Knight M Dunn AK Hightower KE Malkakorpi S Musgrave JR Neu M Rowland P Shea RL Smith JL Somers DO Thomas SA Thompson G Wang R 《Bioorganic & medicinal chemistry letters》2007,17(5):1296-1301
The identification and exploration of a novel, potent and selective series of N-(3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3 kinases is described. Compounds 5a and 11a were identified as potent inhibitors of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK) family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3-cyano substituent forming an H-bond acceptor interaction with the hinge region of the ATP-binding site. 相似文献
142.
Chang CW Tsai WH Chuang WJ Lin YS Wu JJ Liu CC Tsai PJ Lin MT 《Journal of biomedical science》2007,14(3):419-427
Summary After streptococcal pyrogenic exotoxin B (SPE B) induces apoptosis, its fate is unknown. Using confocal time-course microscopy
at 37 °C, we detected green fluorescence 20 min after adding FITC-SPE B. Orange fluorescence, an indication of co-localization
of SPE B with lysosomes which were labeled with a red fluorescent probe, was maximal at 40 min and absent by 60 min. SPE B
was co-precipitated with clathrin, which is consistent with endocytotic involvement. Western blotting assay also indicated
that uptake of SPE B was maximal at 40 min and disappeared after 60 min. However, in the presence of chloroquine, a lysosome
inhibitor, the uptake of SPE B was not detectable. The disappearance of TCA-precipitated FITC-SPE B was parallel to the appearance
of TCA soluble FITC-SPE B; in the presence of chloroquine, however, no SPE B degradation occurred. Chloroquine increased the
level of SPE B-induced apoptosis by inhibiting the degradation of SPE B. These results suggest that the internalization and
degradation of SPE B in cells may be a host defense system that removes toxic substances by sacrificing the exposed cells. 相似文献
143.
Background
Alternative splicing (AS) has been regarded capable of altering selection pressure on protein subsequences. Particularly, the frequency of reading frame preservation (FRFP), as a measure of selection pressure, has been reported to be higher in alternatively spliced exons (ASEs) than in constitutively spliced exons (CSEs). However, recently it has been reported that different ASE types – simple and complex ASEs – may be subject to opposite selection forces. Therefore, it is necessary to re-evaluate the evolutionary effects of such splicing patterns on frame preservation. 相似文献144.
Rice SPX-Major Facility Superfamily3, a Vacuolar Phosphate Efflux Transporter,Is Involved in Maintaining Phosphate Homeostasis in Rice 总被引:1,自引:0,他引:1
145.
146.
Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells
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Margarida Ruas Lianne C Davis Cheng-Chang Chen Anthony J Morgan Kai-Ting Chuang Timothy F Walseth Christian Grimm Clive Garnham Trevor Powell Nick Platt Frances M Platt Martin Biel Christian Wahl-Schott John Parrington Antony Galione 《The EMBO journal》2015,34(13):1743-1758
The second messenger NAADP triggers Ca2+ release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2−/−), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca2+ responses as assessed by single-cell Ca2+ imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on TPCs. In Tpcn1/2−/− cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca2+-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca2+ release. High-affinity [32P]NAADP binding still occurs in Tpcn1/2−/− tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca2+-permeable channels indispensable for NAADP signalling. 相似文献
147.
Glutamine and intestinal barrier function 总被引:1,自引:0,他引:1
Bin Wang Guoyao Wu Zhigang Zhou Zhaolai Dai Yuli Sun Yun Ji Wei Li Weiwei Wang Chuang Liu Feng Han Zhenlong Wu 《Amino acids》2015,47(10):2143-2154
148.
149.
Amy A. Connolly Kenji Sugioka Chien-Hui Chuang Joshua B. Lowry Bruce Bowerman 《The Journal of cell biology》2015,210(6):917-932
During oocyte meiotic cell division in many animals, bipolar spindles assemble in the absence of centrosomes, but the mechanisms that restrict pole assembly to a bipolar state are unknown. We show that KLP-7, the single mitotic centromere–associated kinesin (MCAK)/kinesin-13 in Caenorhabditis elegans, is required for bipolar oocyte meiotic spindle assembly. In klp-7(−) mutants, extra microtubules accumulated, extra functional spindle poles assembled, and chromosomes frequently segregated as three distinct masses during meiosis I anaphase. Moreover, reducing KLP-7 function in monopolar klp-18(−) mutants often restored spindle bipolarity and chromosome segregation. MCAKs act at kinetochores to correct improper kinetochore–microtubule (k–MT) attachments, and depletion of the Ndc-80 kinetochore complex, which binds microtubules to mediate kinetochore attachment, restored bipolarity in klp-7(−) mutant oocytes. We propose a model in which KLP-7/MCAK regulates k–MT attachment and spindle tension to promote the coalescence of early spindle pole foci that produces a bipolar structure during the acentrosomal process of oocyte meiotic spindle assembly. 相似文献
150.
Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis
Receptor-interacting protein 140 (RIP140) is abundantly expressed in mature adipocyte and modulates gene expression involved in lipid and glucose metabolism. Protein kinase C epsilon and protein arginine methyltransferase 1 can sequentially stimulate RIP140 phosphorylation and then methylation, thereby promoting its export to the cytoplasm. Here we report a lipid signal triggering cytoplasmic accumulation of RIP140, and a new functional role for cytoplasmic RIP140 in adipocyte to regulate lipolysis. Increased lipid content, particularly an elevation in diacylglycerol levels, promotes RIP140 cytoplasmic accumulation and increased association with lipid droplets (LDs) by its direct interaction with perilipin. By interacting with RIP140, perilipin more efficiently recruits hormone-sensitive lipase (HSL) to LDs and enhances adipose triglyceride lipase (ATGL) forming complex with CGI-58, an activator of ATGL. Consequentially, HSL can more readily access its substrates, and ATGL is activated, ultimately enhancing lipolysis. In adipocytes, blocking cytoplasmic RIP140 accumulation reduces basal and isoproterenol-stimulated lipolysis and the pro-inflammatory potential of their conditioned media (i.e. activating NF-κB and inflammatory genes in macrophages). These results show that in adipocytes with high lipid contents, RIP140 increasingly accumulates in the cytoplasm and enhances triglyceride catabolism by directly interacting with perilipin. The study suggests that reducing nuclear export of RIP140 might be a useful means of controlling adipocyte lipolysis. 相似文献