全文获取类型
收费全文 | 6582篇 |
免费 | 548篇 |
国内免费 | 5篇 |
出版年
2023年 | 28篇 |
2022年 | 65篇 |
2021年 | 107篇 |
2020年 | 75篇 |
2019年 | 87篇 |
2018年 | 108篇 |
2017年 | 126篇 |
2016年 | 169篇 |
2015年 | 291篇 |
2014年 | 397篇 |
2013年 | 440篇 |
2012年 | 559篇 |
2011年 | 499篇 |
2010年 | 336篇 |
2009年 | 289篇 |
2008年 | 342篇 |
2007年 | 378篇 |
2006年 | 356篇 |
2005年 | 335篇 |
2004年 | 305篇 |
2003年 | 301篇 |
2002年 | 278篇 |
2001年 | 69篇 |
2000年 | 57篇 |
1999年 | 63篇 |
1998年 | 81篇 |
1997年 | 60篇 |
1996年 | 59篇 |
1995年 | 46篇 |
1994年 | 60篇 |
1993年 | 48篇 |
1992年 | 74篇 |
1991年 | 45篇 |
1990年 | 48篇 |
1989年 | 47篇 |
1988年 | 31篇 |
1987年 | 37篇 |
1986年 | 23篇 |
1985年 | 30篇 |
1984年 | 40篇 |
1983年 | 33篇 |
1982年 | 31篇 |
1981年 | 36篇 |
1980年 | 19篇 |
1977年 | 16篇 |
1976年 | 19篇 |
1975年 | 21篇 |
1974年 | 28篇 |
1973年 | 16篇 |
1972年 | 20篇 |
排序方式: 共有7135条查询结果,搜索用时 15 毫秒
961.
In 1972, Brazeau et al. isolated somatostatin (somatotropin release-inhibiting factor, SRIF), a cyclic polypeptide with two biologically active isoforms (SRIF-14 and SRIF-28). This event prompted the successful quest for SRIF receptors. Then, nearly a quarter of a century later, it was announced that a neuropeptide, to be named cortistatin (CST), had been cloned, bearing strong resemblance to SRIF. Evidence of special CST receptors never emerged, however. CST rather competed with both SRIF isoforms for specific receptor binding. And binding to the known subtypes with affinities in the nanomolar range, it has therefore been acknowledged to be a third endogenous ligand at SRIF receptors.This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing the characteristic seven-transmembrane-segment (STMS) topography. Years of intensive research have resulted in cloning of five receptor subtypes (sst1-sst5), one of which is represented by two splice variants (sst2A and sst2B). The individual subtypes, functionally coupled to the effectors of signal transduction, are differentially expressed throughout the mammalian organism, with corresponding differences in physiological impact. It is evident that receptor function, from a physiological point of view, cannot simply be reduced to the accumulated operations of individual receptors. Far from being isolated functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst2 and sst5 receptors) in characteristic proportions. In other words, levels of individual receptor subtypes are highly cell-specific and vary with the co-expression of different-ligand receptors. However, the question is how to quantify the relative contributions of individual receptor subtypes to the integration of transduced signals, ultimately the result of collective receptor activity. The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo- and heterodimerisation, let alone oligomerisation. Theoretically, this phenomenon adds a novel series of functional megareceptors/super-receptors, with varied pharmacological profiles, to the catalogue of monomeric receptor subtypes isolated and cloned in the past. SRIF analogues include both peptides and non-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype-selective analogues. Several have become available. 相似文献
962.
Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans. 总被引:10,自引:0,他引:10
Lars Nybo Kirsten M?ller Stefanos Volianitis Bodil Nielsen Niels H Secher 《Journal of applied physiology》2002,93(1):58-64
The development of hyperthermia during prolonged exercise in humans is associated with various changes in the brain, but it is not known whether the cerebral metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance-trained subjects completed two exercise bouts on a cycle ergometer. The gCBF and cerebral metabolic rates of oxygen, glucose, and lactate were determined with the Kety-Schmidt technique after 15 min of exercise when core temperature was similar across trials, and at the end of exercise, either when subjects remained normothermic (core temperature = 37.9 degrees C; control) or when severe hyperthermia had developed (core temperature = 39.5 degrees C; hyperthermia). The gCBF was similar after 15 min in the two trials, and it remained stable throughout control. In contrast, during hyperthermia gCBF decreased by 18% and was therefore lower in hyperthermia compared with control at the end of exercise (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P < 0.05). Concomitant with the reduction in gCBF, there was a proportionally larger increase in the arteriovenous differences for oxygen and glucose, and the cerebral metabolic rate was therefore higher at the end of the hyperthermic trial compared with control. The hyperthermia-induced lowering of gCBF did not alter cerebral lactate release. The hyperthermia-induced reduction in exercise cerebral blood flow seems to relate to a concomitant 18% lowering of arterial carbon dioxide tension, whereas the higher cerebral metabolic rate of oxygen may be ascribed to a Q(10) (temperature) effect and/or the level of cerebral neuronal activity associated with increased exertion. 相似文献
963.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a membrane-bound glycoprotein localized in the endoplasmic reticulum. This enzyme has a key role in regulating local tissue glucocorticoid concentration, acting in vivo predominantly as an oxidoreductase. Previous attempts to purify the native enzyme have yielded a protein without reductase activity. To facilitate detailed studies on its structure and regulation, we have developed a method to purify the full-length human and rat 11β-HSD1 with retention of their natural oxidoreductase activities. This procedure involved recombinant expression of these histidine-tagged enzymes in the yeast Pichia pastoris; large-scale culturing in a fermentor; and single-step purification by metal affinity chromatography. Both enzymes were 90–95% pure and exhibited dehydrogenase and reductase activities with KM values in agreement with those reported in the literature. 相似文献
964.
Jesper Stagegaard Marten Srensen Lars Peter Kvist 《Perspectives in Plant Ecology, Evolution and Systematics》2002,5(2):103
Extractions/applications of plant-resources were investigated in Mestizo communities in the Jenaro Herrera district, Peruvian Amazon. Knowledge differences between genders on forest resource uses were also examined. Two methods were applied: (1) a forest survey based on structured interviews of ten informants on potential uses of 334 pre-selected trees and lianas in permanent sample plots, and interviews of 20 male and female informants concerning potential uses of 85 trees and lianas; and (2) a household survey recording extracted materials in or near the dwellings of 73 families. The conclusions are: (i) most forest products are extracted from a limited number of species, whereas a large number of species is mentioned as important/potentially useful for identical purposes; (ii) coherence exists between extracted species and their abundance in easily accessible forest formations; (iii) knowledge of forest resources is gender correlated; and (iv) a combination of methods for collection of information on use and extraction of plant resources provides more detailed and profound results than using each method separately. 相似文献
965.
Improved nitrogen removal by application of new nitrogen-cycle bacteria 总被引:14,自引:0,他引:14
Jetten Mike S.M. Schmid Markus Schmidt Ingo Wubben Mariska van Dongen Udo Abma Wiebe Sliekers Olav Revsbech Niels Peter Beaumont Hubertus J.E. Ottosen Lars Volcke Eveline Laanbroek H.J. Campos-Gomez Jose Luis Cole Jeff van Loosdrecht Mark Mulder Jan Willem Fuerst John Richardson David van de Pas Katinka Mendez-Pampin Ramon Third Katie Cirpus Irina van Spanning Rob Bollmann Annette Nielsen Lars Peter den Camp Huub Op Schultz Carl Gundersen Jens Vanrolleghem Peter Strous Marc Wagner Michael Kuenen J. Gijs 《Reviews in Environmental Science and Biotechnology》2002,1(1):51-63
In order to meet increasingly stringentEuropean discharge standards, new applicationsand control strategies for the sustainableremoval of ammonia from wastewater have to beimplemented. In this paper we discuss anitrogen removal system based on the processesof partial nitrification and anoxic ammoniaoxidation (anammox). The anammox process offersgreat opportunities to remove ammonia in fullyautotrophic systems with biomass retention. Noorganic carbon is needed in such nitrogenremoval system, since ammonia is used aselectron donor for nitrite reduction. Thenitrite can be produced from ammonia inoxygen-limited biofilm systems or in continuousprocesses without biomass retention. Forsuccessful implementation of the combinedprocesses, accurate biosensors for measuringammonia and nitrite concentrations, insight inthe complex microbial communities involved, andnew control strategies have to be developed andevaluated. 相似文献
966.
Patch use theory predicts that herbivores perceive food as patches and spend more time in high quality patches, i.e. feeding sites providing a high net rate of intake of energy and/or limiting nutrients. The herbivores should accordingly not discriminate among food items in such high quality patches, and food items should thus be eaten in proportion to availability. In contrast, classical diet theory assumes food selection to take place at the level of individual plants, and predicts that the forager should concentrate on the most profitable item until availability drops below some critical threshold.
Here we address how the spatial distribution of European aspen Populus tremula , a highly preferred browse species, affects the selectivity by moose Alces alces at the patch and the tree level. The study was performed in a managed boreal forest landscape in coastal northern Sweden, where aspen occurs highly aggregated almost exclusively in discrete patches. We compared moose' selectivity for aspen and browsing intensity on aspen ramets and other browse species in aspen patches versus at randomly located sites.
Random sites and aspen stands were utilised equally by moose in terms of overall use of forage. There was no difference in total coverage of forage species and relative moose density. Selectivity for aspen was stronger at random sites than at aspen sites, and the browsing intensity on aspen was similar. We conclude that moose did not perceive aspen stands as discrete patches, and used aspen ramets more in accordance with diet theory. These findings agree with the idea that large generalist herbivores strive to maintain a mixed and balanced diet, causing rare species to be over-utilised (negative frequency-dependent food selection). By such selective feeding, moose may reinforce the aggregated distribution of aspen in the managed boreal forest landscape. 相似文献
Here we address how the spatial distribution of European aspen Populus tremula , a highly preferred browse species, affects the selectivity by moose Alces alces at the patch and the tree level. The study was performed in a managed boreal forest landscape in coastal northern Sweden, where aspen occurs highly aggregated almost exclusively in discrete patches. We compared moose' selectivity for aspen and browsing intensity on aspen ramets and other browse species in aspen patches versus at randomly located sites.
Random sites and aspen stands were utilised equally by moose in terms of overall use of forage. There was no difference in total coverage of forage species and relative moose density. Selectivity for aspen was stronger at random sites than at aspen sites, and the browsing intensity on aspen was similar. We conclude that moose did not perceive aspen stands as discrete patches, and used aspen ramets more in accordance with diet theory. These findings agree with the idea that large generalist herbivores strive to maintain a mixed and balanced diet, causing rare species to be over-utilised (negative frequency-dependent food selection). By such selective feeding, moose may reinforce the aggregated distribution of aspen in the managed boreal forest landscape. 相似文献
967.
Olga G?ransson Svante Resj? Lars R?nnstrand Vincent Manganiello Eva Degerman 《Cellular signalling》2002,14(2):175-182
The mechanism of activation for protein kinase B (PKB), an important target for insulin signaling, has been scarcely investigated in primary cells. In this study, we have characterized the insulin-induced phosphorylation and activation of PKB beta in primary rat adipocytes. Insulin stimulation resulted in a translocation of PKB beta from cytosol to membranes, and phosphorylation and activation of PKB beta. Phosphoamino acid analysis and phosphopeptide mapping demonstrated that the phosphorylation occurred mainly on serines, also when using calyculin A, and that these were localized within one major phosphopeptide. Radiosequencing showed that the radioactivity was released in Cycle No. 7. In addition, the peptide was specifically immunoprecipitated from a tryptic digest of PKB beta using the anti-phospho-PKB (Ser-473) antibody. Taken together, these results show that rat adipocyte PKB beta mainly is phosphorylated on Ser-474 in response to insulin stimulation, in contrast to previous studies in human embryonic kidney (HEK) 293 cells demonstrating, in addition, phosphorylation of Thr-309. 相似文献
968.
Giedre Grigelioniene Jacqueline Schoumans Lo Neumeyer Sten Ivarsson Ole Eklöf Ove Enkvist Paul Tordai Inger Fosdal Anne Myhre Otto Westphal Nils Nilsson Maria Elfving Ian Ellis Britt-Marie Anderlid Ingegerd Fransson Isabel Tapia-Paez Magnus Nordenskjöld Lars Hagenäs Jan P. Dumanski 《Human genetics》2001,109(5):551-558
Dyschondrosteosis (DCO; also called Léri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis, fluorescence in situ hybridisation (FISH), Southern blotting, direct sequencing and fibre-FISH analyses. This was combined with auxological examination of the probands and their family members. Evaluation of the auxological data showed a wide intra- and interfamilial phenotype variability in DCO. Out of 28 DCO probands, 22 (79%) were shown to have mutations in the SHOX gene. Sixteen unrelated DCO families had SHOX gene deletions. Four novel DCO-associated mutations were found in different families. In two additional DCO families, the previously described nonsense mutation (Arg195Stop) was detected. We conclude that mutations in the SHOX gene are the major factor in the pathogenesis of DCO. In a female proband with severe IMD and her unaffected sister, we detected an intrachromosomal duplication of the SHOX gene. 相似文献
969.