全文获取类型
收费全文 | 167篇 |
免费 | 35篇 |
出版年
2022年 | 4篇 |
2020年 | 1篇 |
2018年 | 1篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 4篇 |
2013年 | 1篇 |
2012年 | 4篇 |
2011年 | 6篇 |
2010年 | 3篇 |
2009年 | 3篇 |
2008年 | 4篇 |
2007年 | 7篇 |
2006年 | 4篇 |
2005年 | 13篇 |
2004年 | 3篇 |
2003年 | 6篇 |
2002年 | 1篇 |
2001年 | 4篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 16篇 |
1990年 | 5篇 |
1989年 | 8篇 |
1988年 | 14篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 4篇 |
1970年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 719 毫秒
81.
Background
Breast cancer cells frequently metastasize to the skeleton and induce extensive bone destruction. Cancer cells produce proteinases, including matrix metalloproteinases (MMPs) and the plasminogen activator system (PAS) which promote invasion of extracellular matrices, but whether these proteinases degrade bone matrix is unclear. To characterize the role that breast cancer cell proteinases play in bone degradation we compared the effects of three human breast cancer cell lines, MDA-MB-231, ZR-75-1 and MCF-7 with those of a normal breast epithelial cell line, HME. The cell lines were cultured atop radiolabelled matrices of either mineralized or non-mineralized bone or type I collagen, the principal organic constituent of bone. 相似文献82.
Molecular identification and reconstitution of depolarization-induced exocytosis monitored by membrane capacitance
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Regulated exocytosis of neurotransmitters at synapses is fast and tightly regulated. It is unclear which proteins constitute the "minimal molecular machinery" for this process. Here, we show that a novel technique of capacitance monitoring combined with heterologous protein expression can be used to reconstitute exocytosis that is fast (<0.5 s) and triggered directly by membrane depolarization in Xenopus oocytes. Testing synaptic proteins, voltage-gated Ca2+ channels, and using botulinum and tetanus neurotoxins established that the expression of a Ca2+ channel together with syntaxin 1A, SNAP-25, and synaptotagmin was sufficient and necessary for the reconstitution of depolarization-induced exocytosis. Similar to synaptic exocytosis, the reconstituted release was sensitive to neurotoxins, modulated by divalent cations (Ca2+, Ba2+, and Sr2+) or channel (Lc-, N-type), and depended nonlinearly on divalent cation concentration. Because of its improved speed, native trigger, and great experimental versatility, this reconstitution assay provides a novel, promising tool to study synaptic exocytosis. 相似文献
83.
Offen D Gilgun-Sherki Y Barhum Y Benhar M Grinberg L Reich R Melamed E Atlas D 《Journal of neurochemistry》2004,89(5):1241-1251
Increasing evidence suggests that enhanced production of reactive oxygen species (ROS) activates the MAP kinases, c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase MAPK (p38). These phosphorylated intermediates at the stress-activated pathway induce expression of matrix metalloproteinases (MMPs), leading to inflammatory responses and pathological damages involved in the etiology of multiple sclerosis (MS). Here we report that N-acetylcysteine amide (AD4) crosses the blood-brain barrier (BBB), chelates Cu(2+), which catalyzes free radical formation, and prevents ROS-induced activation of JNK, p38 and MMP-9. In the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, oral administration of AD4 drastically reduced the clinical signs, inflammation, MMP-9 activity, and protected axons from demylination damages. In agreement with the in vitro studies, we propose that ROS scavenging by AD4 in MOG-treated animals prevented MMP's induction and subsequent damages through inhibition of MAPK pathway. The low toxicity of AD4 coupled with BBB penetration makes this compound an excellent potential candidate for the therapy of MS and other neurodegenerative disorders. 相似文献
84.
Walther RF Atlas E Carrigan A Rouleau Y Edgecombe A Visentin L Lamprecht C Addicks GC Haché RJ Lefebvre YA 《The Journal of biological chemistry》2005,280(17):17549-17561
85.
We have used an electrophysiological assay to investigate the functional interaction of syntaxin 1A and SNAP-25 with the class C, L-type, and the class B, N-type, voltage-sensitive calcium channels. Co-expression of syntaxin 1A with the pore-forming subunits of the L- and N-type channels in Xenopus oocytes generates a dramatic inhibition of inward currents (>60%) and modifies the rate of inactivation (tau) and steady-state voltage dependence of inactivation. Syntaxin 1-267, which lacks the transmembrane region (TMR), and syntaxin 2 do not modify channel properties, suggesting that the syntaxin 1A interaction site resides predominantly in the TMR. Co-expression of SNAP-25 significantly modifies the gating properties of L- and N-type channels and displays modest inhibition of current amplitude. Syntaxin 1A and SNAP-25 combined restore the syntaxin-inhibited N-type inward current but not the reduced rate of inactivation. Hence, a distinct interaction of a putative syntaxin 1A-SNAP-25 complex with the channel is apparent, consistent with the formation of a synaptosomal SNAP receptors (SNAREs) complex. The in vivo functional reconstitution: (i) establishes the proximity of the SNAREs to calcium channels; (ii) provides new insight into a potential regulatory role for the two SNAREs in controlling calcium influx through N- and L-type channels; and (iii) may suggest a pivotal role for calcium channels in the secretion process. 相似文献
86.
Volume 61, no. 4, p. 1211, column 2, line 40: this sentence should read as follows. "The viable-culture methods for Legionella sp. detection, however, often fail, and the Centers for Disease Control and Prevention has turned, when necessary, to PCR for epidemiological investigations of Legionnaires' disease and Pontiac fever (19)." Line 46: "(6)" should read "(11)." [This corrects the article on p. 1208 in vol. 61.]. 相似文献
87.
Glass-fiber paper chromatography of vitamin E 总被引:1,自引:0,他引:1
88.
Host plant and habitat preference of the endangered Euphydryas maturna (Lepidoptera: Nymphalidae): evidence from northern Europe
下载免费PDF全文
![点击此处可从《Ecological Entomology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. The aim of the present study was to evaluate host plant and habitat preferences in the Estonian populations of Euphydryas maturna, a regionally polyphagous but often locally specialised butterfly endangered in most parts of its European range. 2. Laboratory trials suggested that Fraxinus excelsior, Viburnum opulus and Melampyrum pratense are plants recognised by ovipositing females as potential hosts. These plants also supported development of the larvae, with the poorest growth performance on M. pratense. 3. Both a transect count‐based habitat occupancy analysis and a country‐wide landscape occupancy analysis revealed the abundance of F. excelsior as the primary determinant of the occurrence of E. maturna. In contrast, the occurrence of E. maturna was not associated with habitats colonised by M. pratense. 4. The results suggest that European ash, F. excelsior, is the main, if not the only, host plant of E. maturna in Estonia. The use of V. opulus cannot be excluded, although, due the relative scarcity of this plant, an important role for it as a determinant of the distribution of E. maturna is unlikely. Melampyrum pratense is not likely an alternative host of E. maturna in Estonia, which contrasts with the situation in neighbouring Finland. 5. This study adds to the evidence of geographical differences in host specialisation in melitaeine butterflies. The results imply that conservation actions should focus on securing the favourable status of the locally used host plant; the populations of F. excelsior are currently threatened by a fungal disease, ash dieback. 相似文献
89.
Isolation of microorganisms capable of degrading isoquinoline under aerobic conditions. 总被引:2,自引:2,他引:0
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Isoquinoline-degrading microbial cultures were isolated from oil- and creosote-contaminated soils. The establishment of initial enrichment cultures required the use of emulsified isoquinoline. Once growth on isoquinoline was established, isoquinoline emulsification was no longer required for utilization of isoquinoline as the sole source of carbon and nitrogen by these cultures. An isoquinoline-degrading Acinetobacter strain was isolated from one of the enrichment cultures. The degradation of isoquinoline was accompanied by the accumulation of a red cell-associated pigment and of 1-hydroxyisoquinoline, which was further degraded to unknown intermediary ring-cleavage products and carbon dioxide. 相似文献
90.
The involvement of a GTP-binding protein (G-protein) in the process of neurotransmitter release was examined using pertussis toxin and cholera toxin. Cholinergic agonists are shown to mediate [3H]noradrenaline release in rat brain slices via a pertussis toxin (1.2 micrograms/ml) sensitive, and cholera toxin (0.5 microgram/ml) insensitive G-protein. An indication for the involvement of a G-protein and phospholipase C activation in the release process was implied from the inhibitory effect of neomycin on K+-, veratridine- and carbachol-induced-norepinephrine release. Depolarizing agents mediate a neomycin-sensitive release, which is not which is not affected either by pertussis toxin or cholera toxin, suggesting a different mode of phospholipase C activation, unlike carbachol-induced release, which is both neomycin and pertussis toxin sensitive. Similarly, a hormone-sensitive carrier activated by phenylephrine not via alpha 1-adrenergic receptors, mediates a non-exocytosis efflux which is not affected by neomycin and is shown to be pertussis toxin-insensitive. The inhibitory action of protein kinase C inhibitors polymyxin B, K252a and H-7 [(1-(5-isoquinolinesulphonyl)-2-methyl-piperazine] on release, strongly suggests its participation in the process. Polymyxin B, a relatively selective protein kinase C inhibitor, inhibited carbachol-induced release (IC50 = 0.53 microM) as well as the K+ and the veratridine induced [3H] noradrenaline release, K252a, an inhibitor of various protein kinases at the ATP site, and H-7, another protein kinase C inhibitor, inhibited carbachol-induced noradrenaline released with IC50 = 35 nM and 3 microM respectively. Consistent with its inability to activate phospholipase C, phenylephrine-induced noradrenaline efflux was unaffected by polymyxin B (greater than 70 microM). These results offer more supportive evidence for a major role played by the dual messengers inositol trisphosphate and diacylglycerol (IP3/DG) in the mechanisms of neuronal release. 相似文献