全文获取类型
收费全文 | 156篇 |
免费 | 2篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 2篇 |
丛书文集 | 1篇 |
现状及发展 | 22篇 |
研究方法 | 21篇 |
综合类 | 112篇 |
自然研究 | 3篇 |
出版年
2022年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 3篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 2篇 |
2012年 | 13篇 |
2011年 | 14篇 |
2010年 | 7篇 |
2009年 | 1篇 |
2008年 | 12篇 |
2007年 | 15篇 |
2006年 | 9篇 |
2005年 | 15篇 |
2004年 | 8篇 |
2003年 | 13篇 |
2002年 | 11篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 3篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1946年 | 5篇 |
排序方式: 共有161条查询结果,搜索用时 93 毫秒
71.
Bodin K Ellmerich S Kahan MC Tennent GA Loesch A Gilbertson JA Hutchinson WL Mangione PP Gallimore JR Millar DJ Minogue S Dhillon AP Taylor GW Bradwell AR Petrie A Gillmore JD Bellotti V Botto M Hawkins PN Pepys MB 《Nature》2010,468(7320):93-97
Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis. 相似文献
72.
J Song C Zhong MA Bonaguidi GJ Sun D Hsu Y Gu K Meletis ZJ Huang S Ge G Enikolopov K Deisseroth B Luscher KM Christian GL Ming H Song 《Nature》2012,489(7414):150-154
Adult neurogenesis arises from neural stem cells within specialized niches. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem cells (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division. Our study identifies a niche cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem cells in response to neuronal activity and experience. 相似文献
73.
The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3 总被引:1,自引:0,他引:1
Cloos PA Christensen J Agger K Maiolica A Rappsilber J Antal T Hansen KH Helin K 《Nature》2006,442(7100):307-311
74.
FMRFamide reverses protein phosphorylation produced by 5-HT and cAMP in Aplysia sensory neurons 总被引:3,自引:0,他引:3
Neurotransmitter can modulate neuronal activity through a variety of second messengers that act on ion channels and other substrate proteins. The most commonly described effector mechanism for second messengers in neurons depends on protein phosphorylation mediated by one of three sets of kinases: the cyclic AMP-dependent protein kinases, the Ca2+-calmodulin-dependent protein kinases, and the Ca2+-phospholipid-dependent protein kinases. In addition, some neurotransmitters and second messengers can also inhibit protein phosphorylation by lowering cAMP levels (either by inhibiting adenylyl cyclase or activating phosphodiesterases). This raises the question: can neurotransmitters also modulate neuronal activity by decreasing protein phosphorylation that is independent of cAMP? Various biochemical experiments show that a decrease in protein phosphorylation can arise through activation of a phosphatase or inhibition of kinases. In none of these cases, however, is the physiological role for the decrease in protein phosphorylation known. Here we report that in Aplysia sensory neurons, the presynaptic inhibitory transmitter FMRFamide decreases the resting levels of protein phosphorylation without altering the level of cAMP. Furthermore, FMRFamide overrides the cAMP-mediated enhancement of transmitter release produced by 5-hydroxytryptamine (5-HT), and concomitantly reverses the cAMP-dependent increase in protein phosphorylation produced by 5-HT. These findings indicate that a receptor-mediated decrease in protein phosphorylation may play an important part in the modulation of neurotransmitter release. 相似文献
75.
Pendás AM Zhou Z Cadiñanos J Freije JM Wang J Hultenby K Astudillo A Wernerson A Rodríguez F Tryggvason K López-Otín C 《Nature genetics》2002,31(1):94-99
The mouse ortholog of human FACE-1, Zmpste24, is a multispanning membrane protein widely distributed in mammalian tissues and structurally related to Afc1p/ste24p, a yeast metalloproteinase involved in the maturation of fungal pheromones. Disruption of the gene Zmpste24 caused severe growth retardation and premature death in homozygous-null mice. Histopathological analysis of the mutant mice revealed several abnormalities, including dilated cardiomyopathy, muscular dystrophy and lipodystrophy. These alterations are similar to those developed by mice deficient in A-type lamin, a major component of the nuclear lamina, and phenocopy most defects observed in humans with diverse congenital laminopathies. In agreement with this finding, Zmpste24-null mice are defective in the proteolytic processing of prelamin A. This deficiency in prelamin A maturation leads to the generation of abnormalities in nuclear architecture that probably underlie the many phenotypes observed in both mice and humans with mutations in the lamin A gene. These results indicate that prelamin A is a specific substrate for Zmpste24 and demonstrate the usefulness of genetic approaches for identifying the in vivo substrates of proteolytic enzymes. 相似文献
76.
According to small subunit ribosomal RNA (ss rRNA) sequence comparisons all known Archaea belong to the phyla Crenarchaeota, Euryarchaeota, and--indicated only by environmental DNA sequences--to the 'Korarchaeota'. Here we report the cultivation of a new nanosized hyperthermophilic archaeon from a submarine hot vent. This archaeon cannot be attached to one of these groups and therefore must represent an unknown phylum which we name 'Nanoarchaeota' and species, which we name 'Nanoarchaeum equitans'. Cells of 'N. equitans' are spherical, and only about 400 nm in diameter. They grow attached to the surface of a specific archaeal host, a new member of the genus Ignicoccus. The distribution of the 'Nanoarchaeota' is so far unknown. Owing to their unusual ss rRNA sequence, members remained undetectable by commonly used ecological studies based on the polymerase chain reaction. 'N. equitans' harbours the smallest archaeal genome; it is only 0.5 megabases in size. This organism will provide insight into the evolution of thermophily, of tiny genomes and of interspecies communication. 相似文献
77.
Chipping away at the chip bias: RNA degradation in microarray analysis 总被引:11,自引:0,他引:11
Auer H Lyianarachchi S Newsom D Klisovic MI Marcucci G Marcucci U Kornacker K 《Nature genetics》2003,35(4):292-293
78.
The oceans represent a significant sink for atmospheric carbon dioxide. Variability in the strength of this sink occurs on interannual timescales, as a result of regional and basin-scale changes in the physical and biological parameters that control the flux of this greenhouse gas into and out of the surface mixed layer. Here we analyse a 13-year time series of oceanic carbon dioxide measurements from station ALOHA in the subtropical North Pacific Ocean near Hawaii, and find a significant decrease in the strength of the carbon dioxide sink over the period 1989-2001. We show that much of this reduction in sink strength can be attributed to an increase in the partial pressure of surface ocean carbon dioxide caused by excess evaporation and the accompanying concentration of solutes in the water mass. Our results suggest that carbon dioxide uptake by ocean waters can be strongly influenced by changes in regional precipitation and evaporation patterns brought on by climate variability. 相似文献
79.
Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9 总被引:10,自引:0,他引:10
Brain-derived neurotrophic factor (BDNF) and other neurotrophins are essential for normal brain function. Many types of neurons in the central nervous system are excited by BDNF or neurotrophin-4/5, an action that has recently been implicated in synaptic plasticity. The mechanisms involved in this transmitter-like action of neurotrophins remains unclear. Here, by screening candidate genes with an antisense messenger RNA expression approach and by co-expressing the receptor tyrosine kinase TrkB and various sodium channels, we demonstrate that the tetrodotoxin-insensitive sodium channel Na(V)1.9 underlies the neurotrophin-evoked excitation. These results establish the molecular basis of neurotrophin-evoked depolarization and reveal a mechanism of ligand-mediated sodium channel activation. 相似文献
80.
应用溶胶-凝胶法制备了中温硫化氢固体氧化物燃料电池的纳米复合质子传导膜。用SEM和EDX对纳米复合膜进行了观察和表征,并与传统工艺制备的电解膜(微米级)的性能进行了比较。探讨了微米级和纳米级的复合Li2SO4+A12O3膜的离子传导性随温度变化规律。与传统的工艺采用相同组分制备的微米级电解膜相比,纳米复合膜的微观结构、致密性、机械强度和离子传导性均得到改善,而最显著改善是膜的离子传导性能。纳米复合Li2SO4+Al2O3膜的中温硫化氢固体氧化物燃料电池的性能较稳定,察觉不到膜两侧的气体穿过膜扩散到另一侧。在750℃和101.13kPa下,电池的最大输出功率密度为135mW·cm^-2,最大电流密度为480mA·cm^-2。 相似文献