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111.
Thakur JK Arthanari H Yang F Pan SJ Fan X Breger J Frueh DP Gulshan K Li DK Mylonakis E Struhl K Moye-Rowley WS Cormack BP Wagner G Näär AM 《Nature》2008,452(7187):604-609
112.
Daniel Kümmel Julia Walter Martin Heck Udo Heinemann Michael Veit 《Cellular and molecular life sciences : CMLS》2010,67(15):2653-2664
Bet3, a transport protein particle component involved in vesicular trafficking, contains a hydrophobic tunnel occupied by
a fatty acid linked to cysteine 68. We reported that Bet3 has a unique self-palmitoylating activity. Here we show that mutation
of arginine 67 reduced self-palmitoylation of Bet3, but the effect was compensated by increasing the pH. Thus, arginine helps
to deprotonate cysteine such that it could function as a nucleophile in the acylation reaction which is supported by the structural
analysis of non-acylated Bet3. Using fluorescence spectroscopy we show that long-chain acyl-CoAs bind with micromolar affinity
to Bet3, whereas shorter-chain acyl-CoAs do not interact. Mutants with a deleted acylation site or a blocked tunnel bind to
Pal-CoA, only the latter with slightly reduced affinity. Bet3 contains three binding sites for Pal-CoA, but their number was
reduced to two in the mutant with an obstructed tunnel, indicating that Bet3 contains binding sites on its surface. 相似文献
113.
Caitlin Collin Frank Hauser Ernesto Gonzalez de Valdivia Shizhong Li Julia Reisenberger Eva M. M. Carlsen Zaid Khan Niels Ø. Hansen Florian Puhm Leif Søndergaard Justyna Niemiec Magdalena Heninger Guilin R. Ren Cornelis J. P. Grimmelikhuijzen 《Cellular and molecular life sciences : CMLS》2013,70(17):3231-3242
Muscarinic acetylcholine receptors (mAChRs) play a central role in the mammalian nervous system. These receptors are G protein-coupled receptors (GPCRs), which are activated by the agonists acetylcholine and muscarine, and blocked by a variety of antagonists. Mammals have five mAChRs (m1–m5). In this study, we cloned two structurally related GPCRs from the fruit fly Drosophila melanogaster, which, after expression in Chinese hamster ovary cells, proved to be muscarinic acetylcholine receptors. One mAChR (the A-type; encoded by gene CG4356) is activated by acetylcholine (EC50, 5 × 10?8 M) and muscarine (EC50, 6 × 10?8 M) and blocked by the classical mAChR antagonists atropine, scopolamine, and 3-quinuclidinyl-benzilate (QNB), while the other (the B-type; encoded by gene CG7918) is also activated by acetylcholine, but has a 1,000-fold lower sensitivity to muscarine, and is not blocked by the antagonists. A- and B-type mAChRs were also cloned and functionally characterized from the red flour beetle Tribolium castaneum. Recently, Haga et al. (Nature 2012, 482: 547–551) published the crystal structure of the human m2 mAChR, revealing 14 amino acid residues forming the binding pocket for QNB. These residues are identical between the human m2 and the D. melanogaster and T. castaneum A-type mAChRs, while many of them are different between the human m2 and the B-type receptors. Using bioinformatics, one orthologue of the A-type and one of the B-type mAChRs could also be found in all other arthropods with a sequenced genome. Protostomes, such as arthropods, and deuterostomes, such as mammals and other vertebrates, belong to two evolutionarily distinct lineages of animal evolution that split about 700 million years ago. We found that animals that originated before this split, such as cnidarians (Hydra), had two A-type mAChRs. From these data we propose a model for the evolution of mAChRs. 相似文献
114.
Fünfschilling U Supplie LM Mahad D Boretius S Saab AS Edgar J Brinkmann BG Kassmann CM Tzvetanova ID Möbius W Diaz F Meijer D Suter U Hamprecht B Sereda MW Moraes CT Frahm J Goebbels S Nave KA 《Nature》2012,485(7399):517-521
Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity. However, the underlying support mechanisms are not understood. Here we identify a metabolic component of axon-glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral nervous system, Cox10 conditional mutants exhibit severe neuropathy with dysmyelination, abnormal Remak bundles, muscle atrophy and paralysis. Notably, perturbing mitochondrial respiration did not cause glial cell death. In the adult central nervous system, we found no signs of demyelination, axonal degeneration or secondary inflammation. Unlike cultured oligodendrocytes, which are sensitive to COX inhibitors, post-myelination oligodendrocytes survive well in the absence of COX activity. More importantly, by in vivo magnetic resonance spectroscopy, brain lactate concentrations in mutants were increased compared with controls, but were detectable only in mice exposed to volatile anaesthetics. This indicates that aerobic glycolysis products derived from oligodendrocytes are rapidly metabolized within white matter tracts. Because myelinated axons can use lactate when energy-deprived, our findings suggest a model in which axon-glia metabolic coupling serves a physiological function. 相似文献
115.
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118.
Zenker M Mayerle J Lerch MM Tagariello A Zerres K Durie PR Beier M Hülskamp G Guzman C Rehder H Beemer FA Hamel B Vanlieferinghen P Gershoni-Baruch R Vieira MW Dumic M Auslender R Gil-da-Silva-Lopes VL Steinlicht S Rauh M Shalev SA Thiel C Ekici AB Winterpacht A Kwon YT Varshavsky A Reis A 《Nature genetics》2005,37(12):1345-1350
Johanson-Blizzard syndrome (OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, multiple malformations such as nasal wing aplasia, and frequent mental retardation. We mapped the disease-associated locus to chromosome 15q14-21.1 and identified mutations, mostly truncating ones, in the gene UBR1 in 12 unrelated families with Johanson-Blizzard syndrome. UBR1 encodes one of at least four functionally overlapping E3 ubiquitin ligases of the N-end rule pathway, a conserved proteolytic system whose substrates include proteins with destabilizing N-terminal residues. Pancreas of individuals with Johanson-Blizzard syndrome did not express UBR1 and had intrauterine-onset destructive pancreatitis. In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury. Our findings indicate that deficiency of UBR1 perturbs the pancreas' acinar cells and other organs, presumably owing to metabolic stabilization of specific substrates of the N-end rule pathway. 相似文献
119.
Carbodiimide fixation for immunohistochemistry: Observations on the fixation of polypeptide hormones
Kendall P. A. Polak Julia M. Pearse A. G. E. 《Cellular and molecular life sciences : CMLS》1971,27(9):1104-1106
Zusammenfassung Wasserlösliche Carbodiimide werden als Fixiermittel für immunohistochemische Untersuchungen vorgeschlagen, da sie die Verwendung von Carboxylgruppen bei der Fixierung erlauben.
This work was supported by grants from the Cancer Research Campaign and the Wellcome Foundation. 相似文献
This work was supported by grants from the Cancer Research Campaign and the Wellcome Foundation. 相似文献
120.
All mammals previously studied take maximal rest or sleep after birth, with the amount gradually decreasing as they grow to adulthood, and adult fruitflies and rats die if they are forcibly deprived of sleep. It has therefore been assumed that sleep is necessary for development and serves a vital function in adults. But we show here that, unlike terrestrial mammals, killer-whale and bottlenose-dolphin neonates and their mothers show little or no typical sleep behaviour for the first postpartum month, avoiding obstacles and remaining mobile for 24 hours a day. We find that neonates and their mothers gradually increase the amount of time they spend resting to normal adult levels over a period of several months, but never exceed these levels. Our findings indicate either that sleep behaviour may not have the developmental and life-sustaining functions attributed to it, or that alternative mechanisms may have evolved in cetaceans. 相似文献