全文获取类型
收费全文 | 134篇 |
免费 | 0篇 |
专业分类
系统科学 | 1篇 |
理论与方法论 | 2篇 |
现状及发展 | 61篇 |
研究方法 | 28篇 |
综合类 | 42篇 |
出版年
2018年 | 2篇 |
2017年 | 1篇 |
2015年 | 1篇 |
2013年 | 1篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2009年 | 2篇 |
2008年 | 6篇 |
2007年 | 2篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 2篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 6篇 |
1974年 | 11篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1970年 | 3篇 |
1969年 | 5篇 |
1968年 | 2篇 |
1966年 | 3篇 |
1962年 | 1篇 |
1960年 | 1篇 |
1957年 | 1篇 |
1956年 | 1篇 |
1954年 | 2篇 |
排序方式: 共有134条查询结果,搜索用时 15 毫秒
111.
Spectrin mutations cause spinocerebellar ataxia type 5 总被引:12,自引:0,他引:12
Ikeda Y Dick KA Weatherspoon MR Gincel D Armbrust KR Dalton JC Stevanin G Dürr A Zühlke C Bürk K Clark HB Brice A Rothstein JD Schut LJ Day JW Ranum LP 《Nature genetics》2006,38(2):184-190
We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling. 相似文献
112.
Christian Feißt Carlo Pergola Marija Rakonjac Antonietta Rossi Andreas Koeberle Gabriele Dodt Marika Hoffmann Christina Hoernig Lutz Fischer Dieter Steinhilber Lutz Franke Gisbert Schneider Olof Rådmark Lidia Sautebin Oliver Werz 《Cellular and molecular life sciences : CMLS》2009,66(16):2759-2771
We previously showed that, in vitro, hyperforin from St. John’s wort (Hypericum perforatum) inhibits 5-lipoxygenase (5-LO), the key enzyme in leukotriene biosynthesis. Here, we demonstrate that hyperforin possesses
a novel and unique molecular pharmacological profile as a 5-LO inhibitor with remarkable efficacy in vivo. Hyperforin (4 mg/kg, i.p.) significantly suppressed leukotriene B4 formation in pleural exudates of carrageenan-treated rats associated with potent anti-inflammatory effectiveness. Inhibition
of 5-LO by hyperforin, but not by the iron-ligand type 5-LO inhibitor BWA4C or the nonredox-type inhibitor ZM230487, was abolished
in the presence of phosphatidylcholine and strongly reduced by mutation (W13A-W75A-W102A) of the 5-LO C2-like domain. Moreover,
hyperforin impaired the interaction of 5-LO with coactosin-like protein and abrogated 5-LO nuclear membrane translocation
in ionomycin-stimulated neutrophils, processes that are typically mediated via the regulatory 5-LO C2-like domain. Together,
hyperforin is a novel type of 5-LO inhibitor apparently acting by interference with the C2-like domain, with high effectiveness
in vivo. 相似文献
113.
K Hoffmann 《Experientia》1979,35(11):1529-1530
In male Djungarian hamsters (Phodopus sungorus) short photoperiods (L/D 8/16) with additional 1- or 5-min light-pulses 8 h after light-off were as effective as long photoperiods (L/D 16/8) in stimulating testicular recrudescence, increase in body weight and moult into summer pelage. The results are discussed with regard to the hypothesis that the pattern of melatonin release from the pineal gland is important in mediating photoperiodic effects in mammals. 相似文献
114.
Zusammenfassung
d-Amphetamin (2–4 mg i.v.) verstärkt bei Neuronen des Tectum opticum der Katze die Reizantwort auf optische Bewegungsreize und vermindert oder beseitigt die während einer Reizfolge auftretende neuronale Adaptation. 相似文献
115.
Summary The prothoracic glands of permanent fifth instar larvae ofLocusta migratoria (moulting blocked by selective X-ray treatment of the hemocytopoietic tissue) are in a state of high activity as evidenced by the rate of incorporation of a labelled amino-acid into the proteins synthesized in these glands. Such permanent larvae apparently synthesize no ecdysone nor ecdysterone. 相似文献
116.
Summary In the Mediterranean field cricket,Gryllus bimaculatus, reproduction is controlled by temperature and the corpus allatum (CA) hormone JH III. In CA of females reared at 24°12°C(168 h) (high reproduction rate) a first peak in JH III synthesis is reached about 4 days earlier than in those of 20°C females (low reproduction rate). Furthermore, in 20°C animals CA activity is low during the entire oviposition period, whereas at 24°12°C high CA activity is found during this period of adult life. The results indicate a stimulation of CA activity and reproduction by thermoperiods around a constant low temperature.Supported by the DFG (SFB 87 A 4). 相似文献
117.
Michael Hoffmann 《Foundations of Science》1999,4(3):271-305
Abductive reasoning takes place in forming``hypotheses' in order to explain ``facts.' Thus, theconcept of abduction promises an understanding ofcreativity in science and learning. It raises,however, also a lot of problems. Some of them will bediscussed in this paper. After analyzing thedifference between induction and abduction (1), Ishall discuss Peirce's claim that there is a ``logic'of abduction (2). The thesis is that this claim can beunderstood, if we make a clear distinction betweeninferential elements and perceptive elements ofabductive reasoning. For Peirce, the creative act offorming explanatory hypotheses and the emergence of``new ideas' belongs exclusively to the perceptive sideof abduction. Thus, it is necessary to study the roleof perception in abductive reasoning (3). A furtherproblem is the question whether there is arelationship between abduction and Peirce's concept of``theorematic reasoning' in mathematics (4). Both formsof reasoning could be connected, because both arebased on perception. The last problem concerns therole of instincts in explaining the success ofabductive reasoning in science, and the questionwhether the concept of instinct might be replaced bymethods of inquiry (5). 相似文献
118.
Selenium (Se) is a nutritional trace mineral essential for various aspects of human health that exerts its effects mainly
through its incorporation into selenoproteins as the amino acid, selenocysteine. Twenty-five selenoprotein genes have been
identified in humans and several selenoproteins are broadly classified as antioxidant enzymes. As progress is made on characterizing
the individual members of this protein family, however, it is becoming clear that their properties and functions are quite
diverse. This review summarizes recent insights into properties of individual selenoproteins such as tissue distribution,
subcellular localization, and regulation of expression. Also discussed are potential roles the different selenoproteins play
in human health and disease. 相似文献
119.
Moran K Backman J Brinkhuis H Clemens SC Cronin T Dickens GR Eynaud F Gattacceca J Jakobsson M Jordan RW Kaminski M King J Koc N Krylov A Martinez N Matthiessen J McInroy D Moore TC Onodera J O'Regan M Pälike H Rea B Rio D Sakamoto T Smith DC Stein R St John K Suto I Suzuki N Takahashi K Watanabe M Yamamoto M Farrell J Frank M Kubik P Jokat W Kristoffersen Y 《Nature》2006,441(7093):601-605
The history of the Arctic Ocean during the Cenozoic era (0-65 million years ago) is largely unknown from direct evidence. Here we present a Cenozoic palaeoceanographic record constructed from >400 m of sediment core from a recent drilling expedition to the Lomonosov ridge in the Arctic Ocean. Our record shows a palaeoenvironmental transition from a warm 'greenhouse' world, during the late Palaeocene and early Eocene epochs, to a colder 'icehouse' world influenced by sea ice and icebergs from the middle Eocene epoch to the present. For the most recent approximately 14 Myr, we find sedimentation rates of 1-2 cm per thousand years, in stark contrast to the substantially lower rates proposed in earlier studies; this record of the Neogene reveals cooling of the Arctic that was synchronous with the expansion of Greenland ice (approximately 3.2 Myr ago) and East Antarctic ice (approximately 14 Myr ago). We find evidence for the first occurrence of ice-rafted debris in the middle Eocene epoch (approximately 45 Myr ago), some 35 Myr earlier than previously thought; fresh surface waters were present at approximately 49 Myr ago, before the onset of ice-rafted debris. Also, the temperatures of surface waters during the Palaeocene/Eocene thermal maximum (approximately 55 Myr ago) appear to have been substantially warmer than previously estimated. The revised timing of the earliest Arctic cooling events coincides with those from Antarctica, supporting arguments for bipolar symmetry in climate change. 相似文献
120.
Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis 总被引:25,自引:0,他引:25
Pepys MB Herbert J Hutchinson WL Tennent GA Lachmann HJ Gallimore JR Lovat LB Bartfai T Alanine A Hertel C Hoffmann T Jakob-Roetne R Norcross RD Kemp JA Yamamura K Suzuki M Taylor GW Murray S Thompson D Purvis A Kolstoe S Wood SP Hawkins PN 《Nature》2002,417(6886):254-259
The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes. 相似文献