全文获取类型
收费全文 | 2768篇 |
免费 | 196篇 |
出版年
2024年 | 2篇 |
2023年 | 23篇 |
2022年 | 62篇 |
2021年 | 103篇 |
2020年 | 77篇 |
2019年 | 87篇 |
2018年 | 95篇 |
2017年 | 91篇 |
2016年 | 120篇 |
2015年 | 176篇 |
2014年 | 201篇 |
2013年 | 231篇 |
2012年 | 263篇 |
2011年 | 244篇 |
2010年 | 152篇 |
2009年 | 97篇 |
2008年 | 175篇 |
2007年 | 130篇 |
2006年 | 140篇 |
2005年 | 100篇 |
2004年 | 92篇 |
2003年 | 75篇 |
2002年 | 66篇 |
2001年 | 12篇 |
2000年 | 17篇 |
1999年 | 22篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 9篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 5篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1975年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有2964条查询结果,搜索用时 15 毫秒
161.
162.
Bruna Gigante Rona J. Strawbridge Ilais Moreno Velasquez Zahra Golabkesh Angela Silveira Anuj Goel Damiano Baldassarre Fabrizio Veglia Elena Tremoli Robert Clarke Hugh Watkins Anders Hamsten Steve E. Humphries Ulf de Faire 《PloS one》2015,10(3)
Variants at the interleukin 6 receptor (IL6R) gene regulate inflammation and are associated with risk of coronary heart disease (CHD). The aim of the present study was to investigate the effects of IL6R haplotypes on circulating levels of inflammatory biomarkers and risk of CHD. We performed a discovery analysis in SHEEP, a myocardial infarction (MI) case control study (n = 2,774) and replicated our results in two large, independent European populations, PROCARDIS, a CHD case control study (n = 7,998), and IMPROVE (n = 3,711) a prospective cardiovascular cohort study. Two major haplotype blocks (rs12083537A/G and rs4075015A/T—block 1; and rs8192282G/A, rs4553185T/C, rs8192284A/C, rs4240872T/C and rs7514452T/C—block 2) were identified in the IL6R gene. IL6R haplotype associations with C-reactive protein (CRP), fibrinogen, IL6, soluble IL6R (sIL6R), IL6, IL8 and TNF-α in SHEEP, CRP and fibrinogen in PROCARDIS and CRP in IMPROVE as well as association with risk of MI and CHD, were analyzed by THESIAS. Haplotypes in block 1 were associated neither with circulating inflammatory biomarkers nor with the MI/CHD risk. Haplotypes in block 2 were associated with circulating levels of CRP, in all three study populations, with fibrinogen in SHEEP and PROCARDIS, with IL8 and sIL6Rin SHEEP and with a modest, non significant, increase (7%) in MI/CHD risk in the three populations studied. Our results indicate that IL6R haplotypes regulate the circulating levels of inflammatory biomarkers. Lack of association with the risk of CHD may be explained by the combined effect of SNPs with opposite effect on the CHD risk, the sample size as well as by structural changes affecting sIL6R stability in the circulation. 相似文献
163.
164.
Fernando Henrique Magalh?es Leonardo Abdala Elias Cristiano Rocha da Silva Felipe Fava de Lima Diana Rezende de Toledo André Fabio Kohn 《PloS one》2015,10(11)
Presynaptic inhibition (PSI) has been shown to modulate several neuronal pathways of functional relevance by selectively gating the connections between sensory inputs and spinal motoneurons, thereby regulating the contribution of the stretch reflex circuitry to the ongoing motor activity. In this study, we investigated whether a differential regulation of Ia afferent inflow by PSI may be associated with the performance of two types of plantarflexion sensoriomotor tasks. The subjects (in a seated position) controlled either: 1) the force level exerted by the foot against a rigid restraint (force task, FT); or 2) the angular position of the ankle when sustaining inertial loads (position task, PT) that required the same level of muscle activation observed in FT. Subjects were instructed to maintain their force/position at target levels set at ~10% of maximum isometric voluntary contraction for FT and 90° for PT, while visual feedback of the corresponding force/position signals were provided. Unconditioned H-reflexes (i.e. control reflexes) and H-reflexes conditioned by electrical pulses applied to the common peroneal nerve with conditioning-to-test intervals of 21 ms and 100 ms (corresponding to D1 and D2 inhibitions, respectively) were evoked in a random fashion. A significant main effect for the type of the motor task (FT vs PT) (p = 0.005, η2
p = 0.603) indicated that PTs were undertaken with lower levels of Ia PSI converging onto the soleus motoneuron pool. Additionally, a significant interaction between the type of inhibition (D1 vs D2) and the type of motor task (FT vs PT) (p = 0.038, η2
p = 0.395) indicated that D1 inhibition was associated with a significant reduction in PSI levels from TF to TP (p = 0.001, η2
p = 0.731), whereas no significant difference between the tasks was observed for D2 inhibition (p = 0.078, η2
p = 0.305). These results suggest that D1 and D2 inhibitions of the soleus H-reflex are differentially modulated during the performance of plantarflexion FT and PT. The reduced level of ongoing PSI during PT suggests that, in comparison to FT, there is a larger reliance on inputs from muscle spindles primary afferents when the neuromuscular system is required to maintain position-controlled plantarflexion contractions. 相似文献
165.
Milena S. Espíndola Leonardo J. G. Lima Luana S. Soares Maira C. Cacemiro Fabiana A. Zambuzi Matheus de Souza Gomes Laurence R. Amaral Valdes R. Bollela Olindo A. Martins-Filho Fabiani G. Frantz 《PloS one》2015,10(12)
Background
Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.Methods
CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).Results
We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.Conclusion
HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group. 相似文献166.
167.
Ricardo J. Soares Magalh?es Maria S. Salamat Lydia Leonardo Darren J. Gray Hélène Carabin Kate Halton Donald P. McManus Gail M. Williams Pilarita Rivera Ofelia Saniel Leda Hernandez Laith Yakob Stephen T. McGarvey Archie C. A. Clements 《PLoS neglected tropical diseases》2015,9(9)
BackgroundIn order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection.Conclusions/SignificanceThis analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon. 相似文献
168.
Peter Braun Gregor Grass Angela Aceti Luigina Serrecchia Alessia Affuso Leonardo Marino Stefania Grimaldi Stefania Pagano Matthias Hanczaruk Enrico Georgi Bernd Northoff Anne Sch?ler Michael Schloter Markus Antwerpen Antonio Fasanella 《PloS one》2015,10(8)
During an anthrax outbreak at the Pollino National Park (Basilicata, Italy) in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA) and next generation Whole Genome Sequencing (WGS). PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis. 相似文献
169.
Renan Idalencio Fabiana Kalichak Jo?o Gabriel Santos Rosa Tiago Acosta de Oliveira Gessi Koakoski Darlan Gusso Murilo Sander de Abreu Ana Cristina Varrone Giacomini Heloísa Helena de Alcantara Barcellos Angelo L. Piato Leonardo José Gil Barcellos 《PloS one》2015,10(10)
The presence of drugs and their metabolites in surface waters and municipal effluents has been reported in several studies, but its impacts on aquatic organisms are not yet well understood. This study investigated the effects of acute exposure to the antipsychotic risperidone on the stress and behavioral responses in zebrafish. It became clear that intermediate concentration of risperidone inhibited the hypothalamic-pituitary-interrenal axis and displayed anxiolytic-like effects in zebrafish. The data presented here suggest that the presence of this antipsychotic in aquatic environments can alter neuroendocrine and behavior profiles in zebrafish. 相似文献
170.
Ivan Enrici Mauro Adenzato Rita B. Ardito Antonia Mitkova Marco Cavallo Maurizio Zibetti Leonardo Lopiano Lorys Castelli 《PloS one》2015,10(6)