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41.
Coumarin-based triazoles were synthesized from 3-azidomethylcoumarin and a terminal acetylenic compound. Uncatalysed thermal conditions result in a mixture of both 1,4- and 1,5-regioisomers or the thermodynamically more stable 1,4-regioisomer, whereas the Cu(I)-catalysed reaction affords only the favourable 1,4-regioisomer. B3LYP/6-31G(d) level of theory has been used to calculate geometry and frequency features of the reactants, transition states (TSs) and products. Computational studies further reveal that 1,4-regioisomeric products are more favourable and also thermodynamically more stable compared to the 1,5-regioisomers. 相似文献
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43.
Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer cells treated with resveratrol 总被引:3,自引:0,他引:3
Mohan J Gandhi AA Bhavya BC Rashmi R Karunagaran D Indu R Santhoshkumar TR 《The Journal of biological chemistry》2006,281(26):17599-17611
Polyphenol phytoalexin (resveratrol), found in grapes and red wine is a strong chemopreventive agent with promising safety records with human consumption and unique forms of cell death induction in a variety of tumor cells. However, the mechanism of resveratrol-induced apoptosis upstream of mitochondria is still not defined. The results from this study suggest that caspase-2 activation occurs upstream of mitochondria in resveratrol-treated cells. The upstream activation of caspase-2 is not dependent on its antioxidant property or NF-kappaB inhibition. The activated caspase-2 triggers mitochondrial apoptotic events by inducing conformational changes in Bax/Bak with subsequent release of cytochrome c, apoptosis-inducing factor, and endonuclease G. Caspase-8 activation seems to be independent of these events and does not appear to be mediated by classical death receptor processing or downstream caspases. Both caspase-2 and caspase-8 contribute toward the mitochondrial translocation of Bid, since neither caspase-8 inhibition nor caspase-2 inhibition could prevent translocation of Bid DsRed into mitochondria. Caspase-2 inhibitors or antisense silencing of caspase-2 prevented cell death induced by resveratrol and partially prevented processing of downstream caspases, including caspase-9, caspase-3, and caspase-8. Studies using mouse embryonic fibroblasts deficient for both Bax and Bak indicate the contribution of both Bax and Bak in mediating cell death induced by resveratrol and the existence of Bax/Bak-independent cell death possibly through caspase-8- or caspase-2-mediated mitochondria-independent downstream caspase processing. 相似文献
44.
Gamma-band (25-140 Hz) oscillations are a hallmark of sensory processing in the forebrain. The optic tectum (OT), a midbrain structure implicated in sensorimotor processing and attention, also exhibits gamma oscillations. However, the origin and mechanisms of these oscillations remain unknown. We discovered that in acute slices of the avian OT, persistent (>100 ms) epochs of large amplitude gamma oscillations can be evoked that closely resemble those recorded in vivo. We found that cholinergic, glutamatergic, and GABAergic mechanisms differentially regulate the structure of the oscillations at various timescales. These persistent oscillations originate in the multisensory layers of the OT and are broadcast to visual layers via the cholinergic nucleus Ipc, providing a potential mechanism for enhancing the processing of visual information within the OT. The finding that the midbrain contains an intrinsic gamma-generating circuit suggests that the OT could use its own oscillatory code to route signals to forebrain networks. 相似文献
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46.
Arumugam K MacNicol MC Wang Y Cragle CE Tackett AJ Hardy LL MacNicol AM 《The Journal of biological chemistry》2012,287(13):10639-10649
Cell cycle re-entry during vertebrate oocyte maturation is mediated through translational activation of select target mRNAs, culminating in the activation of mitogen-activated protein kinase and cyclin B/cyclin-dependent kinase (CDK) signaling. The temporal order of targeted mRNA translation is crucial for cell cycle progression and is determined by the timing of activation of distinct mRNA-binding proteins. We have previously shown in oocytes from Xenopus laevis that the mRNA-binding protein Musashi targets translational activation of early class mRNAs including the mRNA encoding the Mos proto-oncogene. However, the molecular mechanism by which Musashi function is activated is unknown. We report here that activation of Musashi1 is mediated by Ringo/CDK signaling, revealing a novel role for early Ringo/CDK function. Interestingly, Musashi1 activation is subsequently sustained through mitogen-activated protein kinase signaling, the downstream effector of Mos mRNA translation, thus establishing a positive feedback loop to amplify Musashi function. The identified regulatory sites are present in mammalian Musashi proteins, and our data suggest that phosphorylation may represent an evolutionarily conserved mechanism to control Musashi-dependent target mRNA translation. 相似文献
47.
Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as "mental time travel" in which the rememberer "jumps back in time." The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus recovering a prior state of temporal context. In vivo single-neuron recordings were taken from the human MTL while epilepsy patients distinguished novel from repeated images in a continuous recognition memory task. The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually-changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel. ? 2012 Wiley Periodicals, Inc. 相似文献
48.
Nadler C Koby S Peleg A Johnson AC Suddala KC Sathiyamoorthy K Smith BE Saper MA Rosenshine I 《PloS one》2012,7(6):e37984
Capsules frequently play a key role in bacterial interactions with their environment. Escherichia coli capsules were categorized as groups 1 through 4, each produced by a distinct mechanism. Etk and Etp are members of protein families required for the production of group 1 and group 4 capsules. These members function as a protein tyrosine kinase and protein tyrosine phosphatase, respectively. We show that Etp dephosphorylates Etk in vivo, and mutations rendering Etk or Etp catalytically inactive result in loss of group 4 capsule production, supporting the notion that cyclic phosphorylation and dephosphorylation of Etk is required for capsule formation. Notably, Etp also becomes tyrosine phosphorylated in vivo and catalyzes rapid auto-dephosphorylation. Further analysis identified Tyr121 as the phosphorylated residue of Etp. Etp containing Phe, Glu or Ala in place of Tyr121 retained phosphatase activity and catalyzed dephosphorylation of Etp and Etk. Although EtpY121E and EtpY121A still supported capsule formation, EtpY121F failed to do so. These results suggest that cycles of phosphorylation and dephosphorylation of Etp, as well as Etk, are involved in the formation of group 4 capsule, providing an additional regulatory layer to the complex control of capsule production. 相似文献
49.
Nguyen TK Arungundram S Tran VM Raman K Al-Mafraji K Venot A Boons GJ Kuberan B 《Molecular bioSystems》2012,8(2):609-614
Heparan sulfate (HS) glucosaminyl 3-O-sulfotranferases sulfate the C3-hydroxyl group of certain glucosamine residues on heparan sulfate. Six different 3-OST isoforms exist, each of which can sulfate very distinct glucosamine residues within the HS chain. Among these isoforms, 3-OST1 has been shown to play a role in generating ATIII-binding HS anticoagulants whereas 3-OST2, 3-OST3, 3-OST4 and 3OST-6 have been shown to play a vital role in generating gD-binding HS chains that permit the entry of herpes simplex virus type 1 into cells. 3-OST5 has been found to generate both ATIII- and gD-binding HS motifs. Previous studies have examined the substrate specificities of all the 3-OST isoforms using HS polysaccharides. However, very few studies have examined the contribution of the epimer configuration of neighboring uronic acid residues next to the target site to 3-OST action. In this study, we utilized a well-defined synthetic oligosaccharide library to examine the substrate specificity of 3-OST3a and compared it to 3-OST1. We found that both 3-OST1 and 3-OST3a preferentially sulfate the 6-O-sulfated, N-sulfoglucosamine when an adjacent iduronyl residue is located to its reducing side. On the other hand, 2-O-sulfation of this uronyl residue can inhibit the action of 3-OST3a on the target residue. The results reveal novel substrate sites for the enzyme actions of 3-OST3a. It is also evident that both these enzymes have promiscuous and overlapping actions that are differentially regulated by iduronyl 2-O-sulfation. 相似文献
50.
Karthik Subramanyan Ye Wu Urmila M. Diwekar Michael Q. Wang 《The International Journal of Life Cycle Assessment》2008,13(3):278-285