全文获取类型
收费全文 | 2543篇 |
免费 | 201篇 |
国内免费 | 15篇 |
出版年
2022年 | 29篇 |
2021年 | 62篇 |
2020年 | 26篇 |
2019年 | 39篇 |
2018年 | 49篇 |
2017年 | 59篇 |
2016年 | 73篇 |
2015年 | 126篇 |
2014年 | 123篇 |
2013年 | 172篇 |
2012年 | 181篇 |
2011年 | 189篇 |
2010年 | 107篇 |
2009年 | 120篇 |
2008年 | 129篇 |
2007年 | 137篇 |
2006年 | 126篇 |
2005年 | 140篇 |
2004年 | 114篇 |
2003年 | 105篇 |
2002年 | 100篇 |
2001年 | 55篇 |
2000年 | 37篇 |
1999年 | 44篇 |
1998年 | 22篇 |
1997年 | 27篇 |
1996年 | 17篇 |
1995年 | 17篇 |
1994年 | 16篇 |
1993年 | 11篇 |
1992年 | 22篇 |
1991年 | 20篇 |
1990年 | 15篇 |
1989年 | 20篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 21篇 |
1985年 | 11篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1981年 | 9篇 |
1980年 | 10篇 |
1979年 | 12篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1973年 | 12篇 |
1971年 | 7篇 |
1970年 | 7篇 |
1968年 | 8篇 |
1967年 | 15篇 |
排序方式: 共有2759条查询结果,搜索用时 15 毫秒
181.
182.
Olivia Lenoir Magali Jasiek Carole Hénique Léa Guyonnet Bj?rn Hartleben Tillmann Bork Anna Chipont Kathleen Flosseau Imane Bensaada Alain Schmitt Jean-Marc Massé Michèle Souyri Tobias B Huber Pierre-Louis Tharaux 《Autophagy》2015,11(7):1130-1145
The glomerulus is a highly specialized capillary tuft, which under pressure filters large amounts of water and small solutes into the urinary space, while retaining albumin and large proteins. The glomerular filtration barrier (GFB) is a highly specialized filtration interface between blood and urine that is highly permeable to small and midsized solutes in plasma but relatively impermeable to macromolecules such as albumin. The integrity of the GFB is maintained by molecular interplay between its 3 layers: the glomerular endothelium, the glomerular basement membrane and podocytes, which are highly specialized postmitotic pericytes forming the outer part of the GFB. Abnormalities of glomerular ultrafiltration lead to the loss of proteins in urine and progressive renal insufficiency, underlining the importance of the GFB. Indeed, albuminuria is strongly predictive of the course of chronic nephropathies especially that of diabetic nephropathy (DN), a leading cause of renal insufficiency. We found that high glucose concentrations promote autophagy flux in podocyte cultures and that the abundance of LC3B II in podocytes is high in diabetic mice. Deletion of Atg5 specifically in podocytes resulted in accelerated diabetes-induced podocytopathy with a leaky GFB and glomerulosclerosis. Strikingly, genetic alteration of autophagy on the other side of the GFB involving the endothelial-specific deletion of Atg5 also resulted in capillary rarefaction and accelerated DN. Thus autophagy is a key protective mechanism on both cellular layers of the GFB suggesting autophagy as a promising new therapeutic strategy for DN. 相似文献
183.
In human-modified environments, ecological traps may result from a preference for low-quality habitat where survival or reproductive success is lower than in high-quality habitat. It has often been shown that low reproductive success for birds in preferred habitat types was due to higher nest predator abundance. However, between-habitat differences in nest predation may only weakly correlate with differences in nest predator abundance. An ecological trap is at work in a farmland bird (Lanius collurio) that recently expanded its breeding habitat into open areas in plantation forests. This passerine bird shows a strong preference for forest habitat, but it has a higher nest success in farmland. We tested whether higher abundance of nest predators in the preferred habitat or, alternatively, a decoupling of nest predator abundance and nest predation explained this observed pattern of maladaptive habitat selection. More than 90% of brood failures were attributed to nest predation. Nest predator abundance was more than 50% higher in farmland, but nest predation was 17% higher in forest. Differences between nest predation on actual shrike nests and on artificial nests suggested that parent shrikes may facilitate nest disclosure for predators in forest more than they do in farmland. The level of caution by parent shrikes when visiting their nest during a simulated nest predator intrusion was the same in the two habitats, but nest concealment was considerably lower in forest, which contributes to explaining the higher nest predation in this habitat. We conclude that a decoupling of nest predator abundance and nest predation may create ecological traps in human-modified environments. 相似文献
184.
San Kyeong Cheolhwan Jeong Homan Kang Hong-Jun Cho Sung-Jun Park Jin-Kyoung Yang Sehoon Kim Hyung-Mo Kim Bong-Hyun Jun Yoon-Sik Lee 《PloS one》2015,10(11)
Superparamagnetic Fe3O4 nanoparticles (NPs) based nanomaterials have been exploited in various biotechnology fields including biomolecule separation. However, slow accumulation of Fe3O4 NPs by magnets may limit broad applications of Fe3O4 NP-based nanomaterials. In this study, we report fabrication of Fe3O4 NPs double-layered silica nanoparticles (DL MNPs) with a silica core and highly packed Fe3O4 NPs layers. The DL MNPs had a superparamagnetic property and efficient accumulation kinetics under an external magnetic field. Moreover, the magnetic field-exposed DL MNPs show quantitative accumulation, whereas Fe3O4 NPs single-layered silica nanoparticles (SL MNPs) and silica-coated Fe3O4 NPs produced a saturated plateau under full recovery of the NPs. DL MNPs are promising nanomaterials with great potential to separate and analyze biomolecules. 相似文献
185.
Magali Teurlai Christophe Eugène Menkès Virgil Cavarero Nicolas Degallier Elodie Descloux Jean-Paul Grangeon Laurent Guillaumot Thérèse Libourel Paulo Sergio Lucio Fran?oise Mathieu-Daudé Morgan Mangeas 《PLoS neglected tropical diseases》2015,9(12)
Background/Objectives
Understanding the factors underlying the spatio-temporal distribution of infectious diseases provides useful information regarding their prevention and control. Dengue fever spatio-temporal patterns result from complex interactions between the virus, the host, and the vector. These interactions can be influenced by environmental conditions. Our objectives were to analyse dengue fever spatial distribution over New Caledonia during epidemic years, to identify some of the main underlying factors, and to predict the spatial evolution of dengue fever under changing climatic conditions, at the 2100 horizon.Methods
We used principal component analysis and support vector machines to analyse and model the influence of climate and socio-economic variables on the mean spatial distribution of 24,272 dengue cases reported from 1995 to 2012 in thirty-three communes of New Caledonia. We then modelled and estimated the future evolution of dengue incidence rates using a regional downscaling of future climate projections.Results
The spatial distribution of dengue fever cases is highly heterogeneous. The variables most associated with this observed heterogeneity are the mean temperature, the mean number of people per premise, and the mean percentage of unemployed people, a variable highly correlated with people''s way of life. Rainfall does not seem to play an important role in the spatial distribution of dengue cases during epidemics. By the end of the 21st century, if temperature increases by approximately 3°C, mean incidence rates during epidemics could double.Conclusion
In New Caledonia, a subtropical insular environment, both temperature and socio-economic conditions are influencing the spatial spread of dengue fever. Extension of this study to other countries worldwide should improve the knowledge about climate influence on dengue burden and about the complex interplay between different factors. This study presents a methodology that can be used as a step by step guide to model dengue spatial heterogeneity in other countries. 相似文献186.
Ryan P. O’Connell Hassan Musa Mario San Martin Gomez Uma Mahesh Avula Todd J. Herron Jerome Kalifa Justus M. B. Anumonwo 《PloS one》2015,10(8)
Background
Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown.Objective
To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes.Methods
We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4–6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs).Results
Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001).Conclusions
SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis. 相似文献187.
The use of hypothermia as a means to save energy is well documented in birds. This energy‐saving strategy is widely considered to occur exclusively at night in diurnally active species. However, recent studies suggest that facultative hypothermia may also occur during the day. Here, we document the use of daytime hypothermia in foraging Black‐capped Chickadees Poecile atricapillus wintering in eastern Canada. We measured the body temperature (Tb) of 126 individuals (plus 48 repeated measures) during a single winter and related values to ambient temperature (Ta) at the time of capture. We also tested whether daytime hypothermia was correlated with the size of body reserves (residuals of mass on structural size and fat score) and levels of metabolic performance (basal metabolic rate and maximum thermogenic capacity). We found that Tb of individual birds was lower when captured at low Ta, reaching values as low as 35.5 °C in actively foraging individuals. Tb was unrelated to metabolic performance or measures of body reserves. Therefore, daytime hypothermia does not result from individuals being unable to maintain Tb during cold spells or to a lack of body reserves. Our data also demonstrated a high level of individual variation in the depth of hypothermia, the causes of which remain to be explored. 相似文献
188.
189.
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
190.
A C Frantz A D McDevitt L C Pope J Kochan J Davison C F Clements M Elmeros G Molina-Vacas A Ruiz-Gonzalez A Balestrieri K Van Den Berge P Breyne E Do Linh San E O ?gren F Suchentrunk L Schley R Kowalczyk B I Kostka D ?irovi? N ?prem M Colyn M Ghirardi V Racheva C Braun R Oliveira J Lanszki A Stubbe M Stubbe N Stier T Burke 《Heredity》2014,113(5):443-453
Although the phylogeography of European mammals has been extensively investigated
since the 1990s, many studies were limited in terms of sampling distribution, the
number of molecular markers used and the analytical techniques employed, frequently
leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic
structure of the European badger (Meles meles) is of interest as it may
result from historic restriction to glacial refugia and/or recent anthropogenic
impact. However, previous studies were based mostly on samples from western Europe,
making it difficult to draw robust conclusions about the location of refugia,
patterns of postglacial expansion and recent demography. In the present study,
continent-wide sampling and analyses with multiple markers provided evidence for two
glacial refugia (Iberia and southeast Europe) that contributed to the genetic
variation observed in badgers in Europe today. Approximate Bayesian computation
provided support for a colonisation of Scandinavia from both Iberian and southeastern
refugia. In the whole of Europe, we observed a decline in genetic diversity with
increasing latitude, suggesting that the reduced diversity in the peripheral
populations resulted from a postglacial expansion processes. Although MSVAR v.1.3
also provided evidence for recent genetic bottlenecks in some of these peripheral
populations, the simulations performed to estimate the method''s power to
correctly infer the past demography of our empirical populations suggested that the
timing and severity of bottlenecks could not be established with certainty. We urge
caution against trying to relate demographic declines inferred using MSVAR with
particular historic or climatological events. 相似文献