全文获取类型
收费全文 | 7310篇 |
免费 | 572篇 |
国内免费 | 1篇 |
专业分类
7883篇 |
出版年
2023年 | 57篇 |
2022年 | 107篇 |
2021年 | 222篇 |
2020年 | 141篇 |
2019年 | 153篇 |
2018年 | 172篇 |
2017年 | 152篇 |
2016年 | 253篇 |
2015年 | 421篇 |
2014年 | 445篇 |
2013年 | 527篇 |
2012年 | 675篇 |
2011年 | 635篇 |
2010年 | 391篇 |
2009年 | 359篇 |
2008年 | 501篇 |
2007年 | 424篇 |
2006年 | 413篇 |
2005年 | 351篇 |
2004年 | 310篇 |
2003年 | 245篇 |
2002年 | 260篇 |
2001年 | 47篇 |
2000年 | 42篇 |
1999年 | 50篇 |
1998年 | 43篇 |
1997年 | 36篇 |
1996年 | 32篇 |
1995年 | 34篇 |
1994年 | 28篇 |
1993年 | 17篇 |
1992年 | 39篇 |
1991年 | 29篇 |
1990年 | 21篇 |
1989年 | 27篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 22篇 |
1985年 | 19篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 12篇 |
1980年 | 15篇 |
1979年 | 7篇 |
1978年 | 9篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1973年 | 9篇 |
排序方式: 共有7883条查询结果,搜索用时 15 毫秒
141.
Nicolas Rochereau Daniel Drocourt Eric Perouzel Vincent Pavot Pierre Redelinghuys Gordon D. Brown Gerard Tiraby Xavier Roblin Bernard Verrier Christian Genin Blaise Corthésy Stéphane Paul 《PLoS biology》2013,11(9)
Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the Cα1 region and glycosylation, more particularly sialic acid residues, are involved in M cell–mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1+ dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases. 相似文献
142.
Nicolas Tête Clémentine Fritsch Eve Afonso Micha?l Coeurdassier Jean-Claude Lambert Patrick Giraudoux Renaud Scheifler 《PloS one》2013,8(6)
Wildlife is exposed to natural (e.g., food availability and quality, parasitism) and anthropogenic stressors (e.g., habitat fragmentation, toxicants). Individual variables (e.g., age, gender) affect behaviour and physiology of animals. Together, these parameters can create both great inter-individual variations in health indicators and interpretation difficulties. We investigated the relevance of body condition and somatic indices (liver, kidneys) as indicators of health status in wood mice (Apodemus sylvaticus, n = 560) captured along a metal pollution gradient in four landscape types (30 sampling squares 500-m sided). The indices were calculated using a recently proposed standard major axis regression instead of an ordinary least square regression. After considering age and gender for the body condition index, no landscape type influence was detected in the indices. However, important index variability was observed between sampling squares; this effect was included as a random effect in linear models. After integrating all individual and environmental variables that may affect the indices, cadmium (Cd) concentrations in both the liver and kidneys were negatively related to body condition and liver indices only for individuals from highly contaminated sites. Lead in the liver was negatively related to the liver index, and Cd in kidneys was positively linked to the kidney index, potentially suggesting metal-induced stress. However, interpretation of these indices as a wildlife ecotoxicology tool should be performed with caution due to the sensitivity of potentially confounding variables (e.g., individual factors and environmental parameters). 相似文献
143.
Céline Hauzy Grégoire Nadin Elsa Canard Isabelle Gounand Nicolas Mouquet Bo Ebenman 《PloS one》2013,8(12)
Resource enrichment can potentially destabilize predator-prey dynamics. This phenomenon historically referred as the "paradox of enrichment" has mostly been explored in spatially homogenous environments. However, many predator-prey communities exchange organisms within spatially heterogeneous networks called metacommunities. This heterogeneity can result from uneven distribution of resources among communities and thus can lead to the spreading of local enrichment within metacommunities. Here, we adapted the original Rosenzweig-MacArthur predator-prey model, built to study the paradox of enrichment, to investigate the effect of regional enrichment and of its spatial distribution on predator-prey dynamics in metacommunities. We found that the potential for destabilization was depending on the connectivity among communities and the spatial distribution of enrichment. In one hand, we found that at low dispersal regional enrichment led to the destabilization of predator-prey dynamics. This destabilizing effect was more pronounced when the enrichment was uneven among communities. In the other hand, we found that high dispersal could stabilize the predator-prey dynamics when the enrichment was spatially heterogeneous. Our results illustrate that the destabilizing effect of enrichment can be dampened when the spatial scale of resource enrichment is lower than that of organismss movements (heterogeneous enrichment). From a conservation perspective, our results illustrate that spatial heterogeneity could decrease the regional extinction risk of species involved in specialized trophic interactions. From the perspective of biological control, our results show that the heterogeneous distribution of pest resource could favor or dampen outbreaks of pests and of their natural enemies, depending on the spatial scale of heterogeneity. 相似文献
144.
Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties. 相似文献
145.
Karl-Frederik Bergeron Tatiana Cardinal Nicolas Pilon 《Journal of visualized experiments : JoVE》2013,(79)
Neural crest cells (NCC) are a transient and multipotent cell population that originates from the dorsal neural tube and migrates extensively throughout the developing vertebrate embryo. In addition to providing peripheral glia and neurons, NCC generate melanocytes as well as most of the cranio-facial skeleton. NCC migration and differentiation is controlled by a combination of their axial origin along the neural tube and their exposure to regionally distinct extracellular cues. Such contribution of extracellular ligands is especially evident during the formation of the enteric nervous system (ENS), a complex interconnected network of neural ganglia that locally controls (among other things) gut muscle movement and intestinal motility. Most of the ENS is derived from a small initial pool of NCC that undertake a long journey in order to colonize - in a rostral to caudal fashion - the entire length of the prospective gut. Among several signaling pathways known to influence enteric NCC colonization, GDNF/RET signaling is recognized as the most important. Indeed, spatiotemporally controlled secretion of the RET ligand GDNF by the gut mesenchyme is chiefly responsible for the attraction and guidance of RET-expressing enteric NCC to and within the embryonic gut. Here, we describe an ex vivo cell migration assay, making use of a transgenic mouse line possessing fluorescently labeled NCC, which allows precise quantification of enteric NCC migration potential in the presence of various growth factors, including GDNF. 相似文献
146.
In Kyoon Lyoo Sujung Yoon Perry F. Renshaw Jaeuk Hwang Sujin Bae Gail Musen Jieun E. Kim Nicolas Bolo Hyeonseok S. Jeong Donald C. Simonson Sun Hea Lee Katie Weinger Jiyoung J. Jung Christopher M. Ryan Yera Choi Alan M. Jacobson 《PloS one》2013,8(8)
Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. 相似文献
147.
Jonas Saugy Nicolas Place Guillaume Y. Millet Francis Degache Federico Schena Grégoire P. Millet 《PloS one》2013,8(6)
We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·1), lactate dehydrogenase (1145±511 UI·L−1), C-Reactive Protein (13.1±7.5 mg·L−1) and myoglobin (449.3±338.2 µg·L−1) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half. 相似文献
148.
Isabelle Giraud Victorien Valette Nicolas Bech Frédéric Grandjean Richard Cordaux 《PloS one》2013,8(10)
Armadillidium vulgare is a terrestrial isopod (Crustacea, Oniscidea) which harbors Wolbachia bacterial endosymbionts. A. vulgare is the major model for the study of Wolbachia-mediated feminization of genetic males in crustaceans. As a consequence of their impact on host sex determination mechanisms, Wolbachia endosymbionts are thought to significantly influence A. vulgare evolution on various grounds, including population genetic structure, diversity and reproduction strategies. To provide molecular tools for examining these questions, we isolated microsatellite loci through 454 pyrosequencing of a repeat-enriched A. vulgare genomic library. We selected 14 markers and developed three polymorphic microsatellite multiplex kits. We tested the kits on two A. vulgare natural populations and found high genetic variation, thereby making it possible to investigate the impact of Wolbachia endosymbionts on A. vulgare nuclear variation at unprecedented resolution. In addition, we tested the transferability of these kits by cross-species amplification in five other terrestrial isopod species harboring Wolbachia endosymbionts. The microsatellite loci showed good transferability in particular in Armadillidium nasatum and Chaetophiloscia elongata, for which these markers represent promising tools for future genetic studies. 相似文献
149.
150.
Habitat use under predation risk: hunting, roads and human dwellings influence the spatial behaviour of roe deer 总被引:1,自引:0,他引:1
Nadège Bonnot Nicolas Morellet Hélène Verheyden Bruno Cargnelutti Bruno Lourtet François Klein A. J. Mark Hewison 《European Journal of Wildlife Research》2013,59(2):185-193
Wildlife populations are subjected to increasing pressure linked to human activities, which introduce multiple stressors. Recently, in addition to direct effects, it has been shown that indirect (non-lethal) effects of predation risk are predominant in many populations. Predation risk is often structured in space and time, generating a heterogeneous “landscape of fear” within which animals can minimize risks by modifying their habitat use. Furthermore, for ungulates, resource quality seems to be positively correlated with human-related sources of risk. We studied the trade-off between access to resources of high-quality and risk-taking by contrasting habitat use of roe deer during daytime with that during nighttime for 94 roe deer in a hunted population. Our first hypothesis was that roe deer should avoid human disturbance by modifying their habitat use during daytime compared to nighttime. Our results supported this, as roe deer mainly used open fields during nighttime, but used more forested habitats during daytime, when human disturbance is higher. Moreover, we found that diel patterns in habitat use were influenced by hunting disturbance. Indeed, the roe deer decreased their use of high-crops during daytime, an important source of cover and food, during the hunting season. The proximity of roads and dwellings also affected habitat use, since roe deer used open fields during daytime to a greater extent when the distance to these sources of disturbance was higher. Hence, our results suggest that roe deer resolve the trade-off between the acquisition of high-quality resources and risk avoidance by modifying their habitat use between day and night. 相似文献