全文获取类型
收费全文 | 4029篇 |
免费 | 344篇 |
国内免费 | 1篇 |
出版年
2023年 | 20篇 |
2022年 | 43篇 |
2021年 | 83篇 |
2020年 | 45篇 |
2019年 | 91篇 |
2018年 | 83篇 |
2017年 | 81篇 |
2016年 | 152篇 |
2015年 | 182篇 |
2014年 | 212篇 |
2013年 | 262篇 |
2012年 | 264篇 |
2011年 | 229篇 |
2010年 | 155篇 |
2009年 | 176篇 |
2008年 | 172篇 |
2007年 | 175篇 |
2006年 | 184篇 |
2005年 | 187篇 |
2004年 | 161篇 |
2003年 | 148篇 |
2002年 | 135篇 |
2001年 | 111篇 |
2000年 | 120篇 |
1999年 | 81篇 |
1998年 | 61篇 |
1997年 | 58篇 |
1996年 | 41篇 |
1995年 | 36篇 |
1994年 | 30篇 |
1993年 | 35篇 |
1992年 | 63篇 |
1991年 | 47篇 |
1990年 | 53篇 |
1989年 | 47篇 |
1988年 | 44篇 |
1987年 | 43篇 |
1986年 | 26篇 |
1985年 | 33篇 |
1984年 | 28篇 |
1983年 | 16篇 |
1982年 | 19篇 |
1981年 | 14篇 |
1980年 | 12篇 |
1979年 | 16篇 |
1978年 | 14篇 |
1977年 | 9篇 |
1976年 | 10篇 |
1975年 | 12篇 |
1968年 | 6篇 |
排序方式: 共有4374条查询结果,搜索用时 15 毫秒
191.
Bruno Rivas-Santiago Julio E. Casta?eda-Delgado Cesar E. Rivas Santiago Matt Waldbrook Irma González-Curiel Juan C. León–Contreras Jose Antonio Enciso-Moreno Victor del Villar Jazmin Mendez-Ramos Robert E. W. Hancock Rogelio Hernandez-Pando 《PloS one》2013,8(3)
Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15–30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB. 相似文献
192.
Meritxell Genovart Jean-Claude Thibault José Manuel Igual Maria del Mar Bauzà-Ribot Corinne Rabouam Vincent Bretagnolle 《PloS one》2013,8(8)
Dispersal is critically linked to the demographic and evolutionary trajectories of populations, but in most seabird species it may be difficult to estimate. Using molecular tools, we explored population structure and the spatial dispersal pattern of a highly pelagic but philopatric seabird, the Cory''s shearwater Calonectris diomedea. Microsatellite fragments were analysed from samples collected across almost the entire breeding range of the species. To help disentangle the taxonomic status of the two subspecies described, the Atlantic form C. d. borealis and the Mediterranean form C. d. diomedea, we analysed genetic divergence between subspecies and quantified both historical and recent migration rates between the Mediterranean and Atlantic basins. We also searched for evidence of isolation by distance (IBD) and addressed spatial patterns of gene flow. We found a low genetic structure in the Mediterranean basin. Conversely, strong genetic differentiation appeared in the Atlantic basin. Even if the species was mostly philopatric (97%), results suggest recent dispersal between basins, especially from the Atlantic to the Mediterranean (aprox. 10% of migrants/generation across the last two generations). Long-term gene flow analyses also suggested an historical exchange between basins (about 70 breeders/generation). Spatial analysis of genetic variation indicates that distance is not the main factor in shaping genetic structure in this species. Given our results we recommend gathering more data before concluded whether these taxa should be treated as two species or subspecies. 相似文献
193.
194.
Purpose
Cardiovascular responses of traditional resistance (TS) training have been extensively explored. However, the fatigue mechanisms associated with an intra-set rest configuration (ISR) have not been investigated. This study compares two modalities of set configurations for resistance exercise that equates work to rest ratios and measures the central and peripheral fatigue in combination with cortical, hemodynamic and cardiovascular measures.Methods
11 subjects performed two isometric knee extension training sessions using TS and ISR configurations. Voluntary activation (VA), single twitch amplitude, low frequency fatigue (LFF), Mwave, motor evoked potential (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF) and heart rate variability were evaluated before and after each training session. During each session beat to beat heart rate, blood pressure and rate pressure product (RPP) were also evaluated.Results
After exercise VA decreased significantly for TS but not for ISR (P < 0.001), single twitch amplitude and LFF values were lower for TS than ISR (P < 0.004), and SICI was reduced only for the TS configuration (P = 0.049). During exercise RPP values were significantly higher for the TS than for ISR (P = 0.001). RPP correlated with VA for TS (r = -.85 P < 0.001) suggesting a relationship between central fatigue and cardiovascular stress.Conclusions
We conclude that ISR induced lower central and peripheral fatigue as well as lower cardiovascular stress in comparison with TS configuration. Our study suggests that set configuration is a key factor in the regulation of the neuromuscular and cardiovascular responses of resistance training. 相似文献195.
Protein markers of Bursaphelenchus xylophilus Steiner & Buhrer, 1934 (Nickle, 1970) populations using quantitative proteomics and character compatibility
下载免费PDF全文
![点击此处可从《Proteomics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sergio Ciordia Lee Robertson Susana C. Arcos María Rosa González María del Carmen Mena Paula Zamora Paulo Vieira Isabel Abrantes Manuel Mota Philippe Castagnone‐Sereno Alfonso Navas 《Proteomics》2016,16(6):1006-1014
The Pine Wood Nematode (PWN) Bursaphelenchus xylophilus is a severe forest pathogen in countries where it has been introduced and is considered a worldwide quarantine organism. In this study, protein markers for differentiating populations of this nematode were identified by studying differences among four selected Iberian and one American population. These populations were compared by quantitative proteomics (iTRAQ). From a total of 2860 proteins identified using the public database from the B. xylophilus genome project, 216 were unambiguous and significantly differentially regulated in the studied populations. Comparisons of their pairwise ratio were statistically treated and supported in order to convert them into discrete character states, suggesting that 141 proteins were not informative as population specific markers. Application of the Character Compatibility methodology on the remaining 75 proteins (belonging to families with different biological functions) excludes 27 which are incompatible among them. Considering only the compatible proteins, the method selects a subset of 30 specific unique protein markers which allowed the compared classification of the Iberian isolates. This approach makes it easier search for diagnostic tools and phylogenetic inference within species and populations of a pathogen exhibiting a high level of genetic diversity. 相似文献
196.
High‐fat diet exacerbates pain‐like behaviors and periarticular bone loss in mice with CFA‐induced knee arthritis
下载免费PDF全文
![点击此处可从《Obesity (Silver Spring, Md.)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Aleyda A. Loredo‐Pérez Carlos E. Montalvo‐Blanco Luis I. Hernández‐González Maricruz Anaya‐Reyes Cecilia Fernández del Valle‐Laisequilla Juan G. Reyes‐García Rosa I. Acosta‐González Arisai Martínez‐Martínez Jaira C. Villarreal‐Salcido Virginia M. Vargas‐Muñoz Enriqueta Muñoz‐Islas Martha B. Ramírez‐Rosas Juan M. Jiménez‐Andrade 《Obesity (Silver Spring, Md.)》2016,24(5):1106-1115
197.
John R. Pearson Federico Zurita Laura Tomás-Gallardo Alfonsa Díaz-Torres María del Carmen Díaz de la Loza Kristian Franze María D. Martín-Bermudo Acaimo González-Reyes 《PLoS genetics》2016,12(1)
The extracellular matrix (ECM) is a pivotal component adult tissues and of many tissue-specific stem cell niches. It provides structural support and regulates niche signaling during tissue maintenance and regeneration. In many tissues, ECM remodeling depends on the regulation of MMP (matrix metalloproteinase) activity by inhibitory TIMP (tissue inhibitors of metalloproteinases) proteins. Here, we report that the only Drosophila timp gene is required for maintaining the normal organization and function of the germline stem cell niche in adult females. timp mutant ovaries show reduced levels of both Drosophila Collagen IV α chains. In addition, tissue stiffness and the cellular organization of the ovarian niche are affected in timp mutants. Finally, loss of timp impairs the ability of the germline stem cell niche to generate new cysts. Our results demonstrating a crucial role for timp in tissue organization and gamete production thus provide a link between the regulation of ECM metabolism and tissue homeostasis. 相似文献
198.
Maria-Luisa del Rio Carlos Fernandez-Renedo Olivier Chaloin Stefanie Scheu Klaus Pfeffer Yasushi Shintani 《MABS-AUSTIN》2016,8(3):478-490
Tumor necrosis factor (TNF)/TNF receptor (TNFR) superfamily members play essential roles in the development of the different phases of the immune response. Mouse LIGHT (TNFSF14) is a type II transmembrane protein with a C-terminus extracellular TNF homology domain (THD) that assembles in homotrimers and regulates the course of the immune responses by signaling through 2 receptors, the herpes virus entry mediator (HVEM, TNFSFR14) and the lymphotoxin β receptor (LTβR, TNFSFR3). LIGHT is a membrane-bound protein transiently expressed on activated T cells, natural killer (NK) cells and immature dendritic cells that can be proteolytically cleaved by a metalloprotease and released to the extracellular milieu. The immunotherapeutic potential of LIGHT blockade was evaluated in vivo. Administration of an antagonist of LIGHT interaction with its receptors attenuated the course of graft-versus-host reaction and recapitulated the reduced cytotoxic activity of LIGHT-deficient T cells adoptively transferred into non-irradiated semiallogeneic recipients. The lack of LIGHT expression on donor T cells or blockade of LIGHT interaction with its receptors slowed down the rate of T cell proliferation and decreased the frequency of precursor alloreactive T cells, retarding T cell differentiation toward effector T cells. The blockade of LIGHT/LTβR/HVEM pathway was associated with delayed downregulation of interleukin-7Rα and delayed upregulation of inducible costimulatory molecule expression on donor alloreactive CD8 T cells that are typical features of impaired T cell differentiation. These results expose the relevance of LIGHT/LTβR/HVEM interaction for the potential therapeutic control of the allogeneic immune responses mediated by alloreactive CD8 T cells that can contribute to prolong allograft survival. 相似文献
199.
200.
Mar Masiá Sergio Padilla Marta Fernández Carmen Rodríguez Ana Moreno Jose A. Oteo Antonio Antela Santiago Moreno Julia del Amo Félix Gutiérrez CoRIS Biobanco 《PloS one》2016,11(4)
ObjectiveWe aimed to assess whether oxidative stress is a predictor of mortality in HIV-infected patients.MethodsWe conducted a nested case-control study in CoRIS, a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Cases were patients who died with available stored plasma samples collected. Two age and sex-matched controls for each case were selected. We measured F2-isoprostanes (F2-IsoPs) and malondialdehyde (MDA) plasma levels in the first blood sample obtained after cohort engagement.Results54 cases and 93 controls were included. Median F2-IsoPs and MDA levels were significantly higher in cases than in controls. When adjustment was performed for age, HIV-transmission category, CD4 cell count and HIV viral load at cohort entry, and subclinical inflammation measured with highly-sensitive C-reactive protein (hsCRP), the association of F2-IsoPs with mortality remained significant (adjusted OR per 1 log10 increase, 2.34 [1.23–4.47], P = 0.009). The association of MDA with mortality was attenuated after adjustment: adjusted OR (95% CI) per 1 log10 increase, 2.05 [0.91–4.59], P = 0.080. Median hsCRP was also higher in cases, and it also proved to be an independent predictor of mortality in the adjusted analysis: OR (95% CI) per 1 log10 increase, 1.39 (1.01–1.91), P = 0.043; and OR (95% CI) per 1 log10 increase, 1.46 (1.07–1.99), P = 0.014, respectively, when adjustment included F2-IsoPs and MDA.ConclusionOxidative stress is a predictor of all-cause mortality in HIV-infected patients. For plasma F2-IsoPs, this association is independent of HIV-related factors and subclinical inflammation. 相似文献