全文获取类型
收费全文 | 9242篇 |
免费 | 593篇 |
国内免费 | 3篇 |
专业分类
9838篇 |
出版年
2024年 | 3篇 |
2023年 | 64篇 |
2022年 | 121篇 |
2021年 | 248篇 |
2020年 | 152篇 |
2019年 | 166篇 |
2018年 | 313篇 |
2017年 | 240篇 |
2016年 | 342篇 |
2015年 | 511篇 |
2014年 | 576篇 |
2013年 | 730篇 |
2012年 | 835篇 |
2011年 | 819篇 |
2010年 | 502篇 |
2009年 | 438篇 |
2008年 | 577篇 |
2007年 | 500篇 |
2006年 | 510篇 |
2005年 | 427篇 |
2004年 | 364篇 |
2003年 | 357篇 |
2002年 | 355篇 |
2001年 | 65篇 |
2000年 | 57篇 |
1999年 | 57篇 |
1998年 | 102篇 |
1997年 | 75篇 |
1996年 | 50篇 |
1995年 | 37篇 |
1994年 | 41篇 |
1993年 | 29篇 |
1992年 | 29篇 |
1991年 | 25篇 |
1990年 | 18篇 |
1989年 | 17篇 |
1988年 | 15篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 6篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1968年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有9838条查询结果,搜索用时 0 毫秒
981.
Human observers are especially sensitive to the actions of conspecifics that match their own actions. This has been proposed to be critical for social interaction, providing the basis for empathy and joint action. However, the precise relation between observed and executed actions is still poorly understood. Do ongoing actions change the way observers perceive others' actions? To pursue this question, we exploited the bistability of depth-ambiguous point-light walkers, which can be perceived as facing towards the viewer or as facing away from the viewer. We demonstrate that point-light walkers are perceived more often as facing the viewer when the observer is walking on a treadmill compared to when the observer is performing an action that does not match the observed behavior (e.g., cycling). These findings suggest that motor processes influence the perceived orientation of observed actions: Acting observers tend to perceive similar actions by conspecifics as oriented towards themselves. We discuss these results in light of the possible mechanisms subtending action-induced modulation of perception. 相似文献
982.
Ana Guarner Cristina Manjón Kevin Edwards Hermann Steller Magali Suzanne Ernesto Sánchez-Herrero 《Developmental biology》2014
The development of the Drosophila leg is a good model to study processes of pattern formation, cell death and segmentation. Such processes require the coordinate activity of different genes and signaling pathways that progressively subdivide the leg territory into smaller domains. One of the main pathways needed for leg development is the Notch pathway, required for determining the proximo-distal axis of the leg and for the formation of the joints that separate different leg segments. The mechanisms required to coordinate such events are largely unknown. We describe here that the zinc finger homeodomain-2 (zfh-2) gene is highly expressed in cells that will form the leg joints and needed to establish a correct size and pattern in the distal leg. There is an early requirement of zfh-2 to establish the correct proximo-distal axis, but zfh-2 is also needed at late third instar to form the joint between the fourth and fifth tarsal segments. The expression of zfh-2 requires Notch activity but zfh-2 is necessary, in turn, to activate Notch targets such as Enhancer of split and big brain. zfh-2 is controlled by the Drosophila activator protein 2 gene and regulates the late expression of tarsal-less. In the absence of zfh-2 many cells ectopically express the pro-apoptotic gene head involution defective, activate caspase-3 and are positive for acridine orange, indicating they undergo apoptosis. Our results demonstrate the key role of zfh-2 in the control of cell death and Notch signaling during leg development. 相似文献
983.
Annarita Poli Ida Romano Paolo Cordella Pierangelo Orlando Barbara Nicolaus Cristina Ceschi Berrini 《Extremophiles : life under extreme conditions》2009,13(6):867-874
A novel aerobe thermophilic endospore-forming bacterium designated strain AF/04T was isolated from thermal mud located in Euganean hot springs, Abano Terme, Padova, Italy. Strain AF/04T was Gram-positive, motile, rod-shaped, occurring in pairs, or filamentous. The isolate grew between 55 and 67°C (optimum
65°C) and at pH 6.0–7.5 (optimum pH 7.2). The strain was aerobic and grew on maltose, trehalose, and sodium acetate as sole
carbon sources. The G + C content of DNA was 53.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that
strain AF/04T falls within the genus Anoxybacillus. Levels of 16S rRNA gene sequence similarity between strain AF/04T and the type strains of recognized Anoxybacillus species ranged from 95 to 99%. Chemotaxonomic data (major isoprenoid quinone–menaquinone-7; major fatty acid iso-C15:0 and anteiso-C17:0) supported the affiliation of strain AF/04T to the genus Anoxybacillus. Based on phenotypic and chemotaxonomic characteristics, 16S rRNA gene sequence analysis and DNA–DNA hybridization data, it was proposed that strain AF/04T (=DSM 17141T = ATCC BAA 1156T) should be placed in the genus Anoxybacillus as the type strain of a novel species, Anoxybacillus thermarum sp. nov. 相似文献
984.
Cristina D. Orrù Claudia Abete M. Dolores Cannas Claudia Mulas Claudia Norfo Antonella Mandas Sarah Vascellari Paolo La Colla Sandra Dessì Alessandra Pani 《Central European Journal of Biology》2010,5(1):31-37
Scrapie is a prion disease for which no means of ante-mortem diagnosis is available. We recently found a relationship between
cell susceptibility to scrapie and altered cholesterol homeostasis. In brains and in skin fibroblasts and peripheral blood
mononuclear cells from healthy and scrapie-affected sheep carrying a scrapie-susceptible genotype, the levels of cholesterol
esters were consistently higher than in tissues and cultures derived from animals with a scrapie-resistant genotype. Here
we show that intracellular accumulation of cholesterol esters (CE) in fibroblasts derived from scrapie-susceptible sheep was
accompanied by parallel alterations in the expression level of acyl-coenzymeA: cholesterol-acyltransferase (ACAT1) and caveolin-1
(Cav-1) that are involved in the pathways leading to intracellular cholesterol esterification and trafficking. Comparative
analysis of cellular prion protein (PrPc) mRNA, showed an higher expression level in cells from animals carrying a susceptible
genotype, with or without Scrapie. These data suggest that CE accumulation in peripheral cells, together with the altered
expression of some proteins implicated in intracellular cholesterol homeostasis, might serve to identify a distinctive lipid
metabolic profile associated with increased susceptibility to develop prion disease following infection. 相似文献
985.
Maria Cristina Sanches Sérvio Pontes Ribeiro Valdnéa Casagrande Dalvi Milton Barbosa da Silva Junior Hildeberto Caldas de Sousa José Pires de Lemos-Filho 《Trees - Structure and Function》2010,24(1):79-88
Cariniana legalis is an emergent tree that reaches the upper canopy in Brazilian Semideciduous Forest. Spatial contrasts in microclimatic conditions
between the upper canopy and understorey in a forest may affect morpho-physiological leaf traits. In order to test the hypothesis
that the upper canopy is more stressful to leaves than a gap environment we compared emergent trees of C. legalis, 28–29 m in height to gap saplings, 6–9 m in height, for the following parameters: leaf area, leaf mass area (LMA the dry
weight:leaf area ratio), leaf thickness, leaf anatomical parameters, stomata conductance, and chlorophyll a fluorescence. Leaves from emergent trees had smaller leaf areas but greater LMA compared to saplings. Leaf thickness, palisade
layer thickness, and stomatal density were higher for emergent trees than for saplings. The opposite pattern was observed
for spongy layer thickness and spongy/palisade ratio. Stomatal conductance was also higher for emergent tree leaves than for
sapling leaves, but the magnitude of depression on stomatal conductance near midday was more pronounced in emergent trees.
The potential quantum yield of photosystem II, as determined by the F
v/F
m ratio was lower for leaves from saplings. The lower values of stomatal conductance, indicating restriction in CO2 diffusion into the mesophyll can be related to higher photoinhibition observed in the saplings. Leaves from emergent trees
and saplings exhibited similar values for apparent electron transport rates and non-photochemical quenching. Our results suggest
that changes in leaf traits could be associated to dry conditions at the upper canopy as well as to the ontogenetic transition
between sapling/emergent tree life stages. 相似文献
986.
Ornella Spadoni Alessio Crestini Paola Piscopo Lorenzo Malvezzi-Campeggi Irene Carunchio Massimo Pieri Cristina Zona Annamaria Confaloni 《Cellular and molecular neurobiology》2009,29(5):635-641
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse
model (Tg SOD1G93A) shows pathological features that closely mimic those seen in ALS patients. An hypothetic link between
AD and ALS was suggested by finding an higher amount of amyloid precursor protein (APP) in the spinal cord anterior horn neurons,
and of Aβ peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer’s
disease, as APP, β- and γ-secretase, in an animal model of ALS, to understand some possible common molecular mechanisms between
these two pathologies. For gene expression analysis, we carried out a quantitative RT-PCR in ALS mice and in transgenic mice
over-expressing human wild-type SOD1 (Tg hSOD1). We found that APP and BACE1 mRNA levels were increased 1.5-fold in cortical
cells of Tg SOD1G93A mice respect to Tg hSOD1, whereas the expression of γ-secretase genes, as PSEN1, PSEN2, Nicastrin, and
APH1a, showed no statistical differences between wild-type and ALS mice. Biochemical analysis carried out by immunostaining
and western blotting, did not show any significant modulation of the protein expression compared to the genes, suggesting
the existence of post-translational mechanisms that modify protein levels. 相似文献
987.
988.
Preferential phosphorylation of R-domain Serine 768 dampens activation of CFTR channels by PKA 总被引:1,自引:0,他引:1 下载免费PDF全文
Csanády L Seto-Young D Chan KW Cenciarelli C Angel BB Qin J McLachlin DT Krutchinsky AN Chait BT Nairn AC Gadsby DC 《The Journal of general physiology》2005,125(2):171-186
CFTR (cystic fibrosis transmembrane conductance regulator), the protein whose dysfunction causes cystic fibrosis, is a chloride ion channel whose gating is controlled by interactions of MgATP with CFTR's two cytoplasmic nucleotide binding domains, but only after several serines in CFTR's regulatory (R) domain have been phosphorylated by cAMP-dependent protein kinase (PKA). Whereas eight R-domain serines have previously been shown to be phosphorylated in purified CFTR, it is not known how individual phosphoserines regulate channel gating, although two of them, at positions 737 and 768, have been suggested to be inhibitory. Here we show, using mass spectrometric analysis, that Ser 768 is the first site phosphorylated in purified R-domain protein, and that it and five other R-domain sites are already phosphorylated in resting Xenopus oocytes expressing wild-type (WT) human epithelial CFTR. The WT channels have lower activity than S768A channels (with Ser 768 mutated to Ala) in resting oocytes, confirming the inhibitory influence of phosphoserine 768. In excised patches exposed to a range of PKA concentrations, the open probability (P(o)) of mutant S768A channels exceeded that of WT CFTR channels at all [PKA], and the half-maximally activating [PKA] for WT channels was twice that for S768A channels. As the open burst duration of S768A CFTR channels was almost double that of WT channels, at both low (55 nM) and high (550 nM) [PKA], we conclude that the principal mechanism by which phosphoserine 768 inhibits WT CFTR is by hastening the termination of open channel bursts. The right-shifted P(o)-[PKA] curve of WT channels might explain their slower activation, compared with S768A channels, at low [PKA]. The finding that phosphorylation kinetics of WT or S768A R-domain peptides were similar provides no support for an alternative explanation, that early phosphorylation of Ser 768 in WT CFTR might also impair subsequent phosphorylation of stimulatory R-domain serines. The observed reduced sensitivity to activation by [PKA] imparted by Ser 768 might serve to ensure activation of WT CFTR by strong stimuli while dampening responses to weak signals. 相似文献
989.
Gorostizaga A Brion L Maloberti P Cornejo Maciel F Podestá EJ Paz C 《Biochemical and biophysical research communications》2005,327(1):23-28
Testicular function is highly dependent on temperature control. In Leydig testicular cells, the signaling pathway activated by heat stress is poorly defined. Here we describe the molecular events triggered by heat shock (HS, 10 min, 45 degrees C) in MA-10 cells. HS produced a rapid and transient activation of ERK1/2 and JNK kinases, and also increased MAP kinase phosphatase-1 (MKP-1) protein and mRNA levels. The effect of HS on MKP-1 messenger reached significance at 15 min, peaked (3.5-fold) at 60 min, and was partially dependent on ERK1/2 activity. The temporal profiles of MKP-1 protein levels and MAPKs phospho-dephosphorylation suggest that MKP-1 induction could contribute to ERK1/2 and JNK inactivation after HS. In summary, this study indicates that the response to heat stress in Leydig cells includes the activation of MAPKs related to cell survival (ERK1/2) and death (JNK), and the induction of a MAPK activity inhibitory loop. 相似文献
990.
Arrais-Silva WW Collhone MC Ayres DC de Souza Souto PC Giorgio S 《Parasitology international》2005,54(1):1-7
In the present study, we evaluated the effects of hyperbaric oxygen (HBO) exposure in both Leishmania amazonensis life stages (promastigotes and amastigotes) and on macrophage cultures infected with the parasite. HBO treatment protocols, which can be tolerated by humans and animals, induced irreversible metabolic damage and affected parasite morphology, growth and ability to transform. The observation that the antioxidant N-acetylcysteine (NAC) prevents some of these deleterious effects indicated an involvement of oxidative stress during parasite HBO exposure. In addition, HBO exposed L. amazonensis-infected macrophage cultures showed reduction of the percentage of infected cells and of the number of intracellular parasites per cell. Thus, the demonstration that HBO, a therapy used in the management of different diseases, is toxic for both L. amazonensis life stages and can alter macrophage susceptibility to the infection encourages further studies of this therapy in animal models of Leishmania infection. 相似文献