全文获取类型
收费全文 | 4440篇 |
免费 | 362篇 |
专业分类
4802篇 |
出版年
2022年 | 36篇 |
2021年 | 61篇 |
2020年 | 44篇 |
2019年 | 39篇 |
2018年 | 69篇 |
2017年 | 57篇 |
2016年 | 111篇 |
2015年 | 162篇 |
2014年 | 177篇 |
2013年 | 261篇 |
2012年 | 335篇 |
2011年 | 347篇 |
2010年 | 206篇 |
2009年 | 207篇 |
2008年 | 291篇 |
2007年 | 285篇 |
2006年 | 282篇 |
2005年 | 250篇 |
2004年 | 240篇 |
2003年 | 250篇 |
2002年 | 246篇 |
2001年 | 46篇 |
2000年 | 41篇 |
1999年 | 47篇 |
1998年 | 61篇 |
1997年 | 40篇 |
1996年 | 39篇 |
1995年 | 37篇 |
1994年 | 36篇 |
1993年 | 29篇 |
1992年 | 28篇 |
1991年 | 21篇 |
1990年 | 29篇 |
1989年 | 20篇 |
1988年 | 15篇 |
1987年 | 16篇 |
1985年 | 19篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1982年 | 17篇 |
1981年 | 17篇 |
1980年 | 11篇 |
1979年 | 16篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 17篇 |
1975年 | 12篇 |
1974年 | 16篇 |
1972年 | 13篇 |
1969年 | 9篇 |
排序方式: 共有4802条查询结果,搜索用时 15 毫秒
91.
92.
Agathe Hess Lianchun Yu Isabelle Klein Marine De Mazancourt Gilles Jebrak Hervé Mal Olivier Brugière Michel Fournier Maurice Courbage Gaelle Dauriat Elisabeth Schouman-Clayes Christine Clerici Laurence Mangin 《PloS one》2013,8(10)
Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings. 相似文献
93.
94.
Audrey Schlernitzauer Catherine Oiry Raphael Hamad Simon Galas Fabienne Cortade Béatrice Chabi Fran?ois Casas Laurence Pessemesse Gilles Fouret Christine Feillet-Coudray Gérard Cros Gérard Cabello Richard Magous Chantal Wrutniak-Cabello 《PloS one》2013,8(11)
Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5–100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases. 相似文献
95.
Frank O. Odhiambo Caryl M. Beynon Sheila Ogwang Mary J. Hamel Olivia Howland Anne M. van Eijk Robyn Norton Nyaguara Amek Laurence Slutsker Kayla F. Laserson Kevin M. De Cock Penelope A. Phillips-Howard 《PloS one》2013,8(11)
Background
Information on trauma-related deaths in low and middle income countries is limited but needed to target public health interventions. Data from a health and demographic surveillance system (HDSS) were examined to characterise such deaths in rural western Kenya.Methods And Findings
Verbal autopsy data were analysed. Of 11,147 adult deaths between 2003 and 2008, 447 (4%) were attributed to trauma; 71% of these were in males. Trauma contributed 17% of all deaths in males 15 to 24 years; on a population basis mortality rates were greatest in persons over 65 years. Intentional causes accounted for a higher proportion of male than female deaths (RR 2.04, 1.37-3.04) and a higher proportion of deaths of those aged 15 to 65 than older people. Main causes in males were assaults (n=79, 25%) and road traffic injuries (n=47, 15%); and falls for females (n=17, 13%). A significantly greater proportion of deaths from poisoning (RR 5.0, 2.7-9.4) and assault (RR 1.8, 1.2-2.6) occurred among regular consumers of alcohol than among non-regular drinkers. In multivariate analysis, males had a 4-fold higher risk of death from trauma than females (Adjusted Relative Risk; ARR 4.0; 95% CI 1.7-9.4); risk of a trauma death rose with age, with the elderly at 7-fold higher risk (ARR 7.3, 1.1-49.2). Absence of care was the strongest predictor of trauma death (ARR 12.2, 9.4-15.8). Trauma-related deaths were higher among regular alcohol drinkers (ARR 1.5, 1.1-1.9) compared with non-regular drinkers.Conclusions
While trauma accounts for a small proportion of deaths in this rural area with a high prevalence of HIV, TB and malaria, preventive interventions such as improved road safety, home safety strategies for the elderly, and curbing harmful use of alcohol, are available and could help diminish this burden. Improvements in systems to record underlying causes of death from trauma are required. 相似文献96.
Géraldine De Muylder Sylvie Daulouède Laurence Lecordier Pierrick Uzureau Yannick Morias Jan Van Den Abbeele Guy Caljon Michel Hérin Philippe Holzmuller Silla Semballa Pierrette Courtois Luc Vanhamme Beno?t Stijlemans Patrick De Baetselier Michael P. Barrett Jillian L. Barlow Andrew N. J. McKenzie Luke Barron Thomas A. Wynn Alain Beschin Philippe Vincendeau Etienne Pays 《PLoS pathogens》2013,9(10)
Background
In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.Methodology/Principal findings
By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.Conclusion
A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity. 相似文献97.
Laurence Drouilhet Camille Mansanet Julien Sarry Kamila Tabet Philippe Bardou Florent Woloszyn Jérome Lluch Grégoire Harichaux Catherine Viguié Danielle Monniaux Loys Bodin Philippe Mulsant Stéphane Fabre 《PLoS genetics》2013,9(9)
Prolific sheep have proven to be a valuable model to identify genes and mutations implicated in female fertility. In the Lacaune sheep breed, large variation in litter size is genetically determined by the segregation of a fecundity major gene influencing ovulation rate, named FecL and its prolific allele FecLL. Our previous work localized FecL on sheep chromosome 11 within a locus of 1.1 Mb encompassing 20 genes. With the aim to identify the FecL gene, we developed a high throughput sequencing strategy of long-range PCR fragments spanning the locus of FecLL carrier and non-carrier ewes. Resulting informative markers defined a new 194.6 kb minimal interval. The reduced FecL locus contained only two genes, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and beta-1,4-N-acetyl-galactosaminyl transferase 2 (B4GALNT2), and we identified two SNP in complete linkage disequilibrium with FecLL. B4GALNT2 appeared as the best positional and expressional candidate for FecL, since it showed an ectopic expression in the ovarian follicles of FecLL/FecLL ewes at mRNA and protein levels. In FecLL carrier ewes only, B4GALNT2 transferase activity was localized in granulosa cells and specifically glycosylated proteins were detected in granulosa cell extracts and follicular fluids. The identification of these glycoproteins by mass spectrometry revealed at least 10 proteins, including inhibin alpha and betaA subunits, as potential targets of B4GALNT2 activity. Specific ovarian protein glycosylation by B4GALNT2 is proposed as a new mechanism of ovulation rate regulation in sheep, and could contribute to open new fields of investigation to understand female infertility pathogenesis. 相似文献
98.
Donato Spoltore Wibren D. Oosterbaan Samira Khelifi John N. Clifford Aurelien Viterisi Emilio Palomares Marc Burgelman Laurence Lutsen Dirk Vanderzande Jean Manca 《Liver Transplantation》2013,3(4):466-471
The non‐geminate recombination of charge carriers in polymer‐fullerene solar cells has been modeled in the last few years with a trap‐assisted recombination model, which states that the apparent recombination order depends on the concentration of trapped charges tailing into the band gap. Higher concentrations of trapped charges lead to higher apparent recombination orders. In this work, the mass fraction f of highly crystalline nanofibrillar P3HT to the total P3HT content in P3HT:PCBM solar cells is consistently varied, controlling the temperature of a nanofibers‐P3HT casting dispersion. A systematic study of the apparent recombination order, measured with a transient photovoltage technique, as a function of f is presented. A correlation is shown between the apparent recombination order, the P3HT crystallinity, and the trap concentration in the band gap measured with an admittance spectroscopy technique. 相似文献
99.
Xinzhong Li Andrew J. Buckton Samuel L. Wilkinson Shibu John Roddy Walsh Tomas Novotny Iveta Valaskova Manu Gupta Laurence Game Paul J R. Barton Stuart A. Cook James S. Ware 《PloS one》2013,8(7)