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排序方式: 共有83条查询结果,搜索用时 15 毫秒
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Domire JS Green JA Lee KG Johnson AD Askwith CC Mykytyn K 《Cellular and molecular life sciences : CMLS》2011,68(17):2951-2960
Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction
underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell
types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout
the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling
proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes
to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization
of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the
translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one
of the BBS proteins, Bbs5, specifically interacts with D1. 相似文献
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Leung JY Bennett WR Herbert RP West AK Lee PR Wake H Fields RD Chuah MI Chung RS 《Cellular and molecular life sciences : CMLS》2012,69(5):809-817
Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of
a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating
regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal
root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application
of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative
effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive
antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated
the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma
and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers,
which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was
performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied
solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study
provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin- and MAPK-dependent mechanism. 相似文献
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Núñez-Ríos Juan E. Sánchez-García Jacqueline Y. Tejeida-Padilla Ricardo 《Systemic Practice and Action Research》2020,33(5):527-559
Systemic Practice and Action Research - This article presents an approach to the problem that small and medium-sized Mexican lodging enterprises face regarding their ability to adapt to changes in... 相似文献
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Vogt G Chapgier A Yang K Chuzhanova N Feinberg J Fieschi C Boisson-Dupuis S Alcais A Filipe-Santos O Bustamante J de Beaucoudrey L Al-Mohsen I Al-Hajjar S Al-Ghonaium A Adimi P Mirsaeidi M Khalilzadeh S Rosenzweig S de la Calle Martin O Bauer TR Puck JM Ochs HD Furthner D Engelhorn C Belohradsky B Mansouri D Holland SM Schreiber RD Abel L Cooper DN Soudais C Casanova JL 《Nature genetics》2005,37(7):692-700
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate. 相似文献
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Jacqueline Broad 《Studies in history and philosophy of science》2007,38(3):493-505
Many scholars point to the close association between early modern science and the rise of rational arguments in favour of the existence of witches. For some commentators, it is a poor reflection on science that its methods so easily lent themselves to the unjust persecution of innocent men and women. In this paper, I examine a debate about witches between a woman philosopher, Margaret Cavendish (1623-1673), and a fellow of the Royal Society, Joseph Glanvill (1636-1680). I argue that Cavendish is the voice of reason in this exchange—not because she supports the modern-day view that witches do not exist, but because she shows that Glanvill’s arguments about witches betray his own scientific principles. Cavendish’s responses to Glanvill suggest that, when applied consistently, the principles of early modern science could in fact promote a healthy scepticism toward the existence of witches. 相似文献
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