全文获取类型
收费全文 | 14256篇 |
免费 | 1192篇 |
国内免费 | 1868篇 |
出版年
2024年 | 27篇 |
2023年 | 220篇 |
2022年 | 310篇 |
2021年 | 877篇 |
2020年 | 593篇 |
2019年 | 735篇 |
2018年 | 683篇 |
2017年 | 509篇 |
2016年 | 684篇 |
2015年 | 999篇 |
2014年 | 1161篇 |
2013年 | 1165篇 |
2012年 | 1467篇 |
2011年 | 1271篇 |
2010年 | 801篇 |
2009年 | 699篇 |
2008年 | 800篇 |
2007年 | 692篇 |
2006年 | 576篇 |
2005年 | 520篇 |
2004年 | 405篇 |
2003年 | 355篇 |
2002年 | 297篇 |
2001年 | 200篇 |
2000年 | 176篇 |
1999年 | 169篇 |
1998年 | 134篇 |
1997年 | 120篇 |
1996年 | 88篇 |
1995年 | 81篇 |
1994年 | 106篇 |
1993年 | 57篇 |
1992年 | 65篇 |
1991年 | 54篇 |
1990年 | 43篇 |
1989年 | 39篇 |
1988年 | 22篇 |
1987年 | 20篇 |
1986年 | 15篇 |
1985年 | 27篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 8篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1966年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 178 毫秒
991.
992.
Moffitt’s theory of delinquency suggests that at-risk youths can be divided into two groups, the adolescence- limited group and the life-course-persistent group, predetermined at a young age, and social interactions between these two groups become important during the adolescent years. We built an agent-based model based on the microscopic interactions Moffitt described: (i) a maturity gap that dictates (ii) the cost and reward of antisocial behavior, and (iii) agents imitating the antisocial behaviors of others more successful than themselves, to find indeed the two groups emerging in our simulations. Moreover, through an intervention simulation where we moved selected agents from one social network to another, we also found that the social network plays an important role in shaping the life course outcome. 相似文献
993.
Influenza vaccines elicit antigen-specific antibodies and immune memory to protect humans from infection with drift variants. However, what supports or limits vaccine efficacy and duration is unclear. Here, we vaccinated healthy volunteers with annual vaccine formulations and investigated the dynamics of T cell, natural killer (NK) cell and antibody responses upon restimulation with heterologous or homologous influenza virus strains. Influenza vaccines induced potential memory NK cells with increased antigen-specific recall IFN-γ responses during the first 6 months. In the absence of significant changes in other NK cell markers (CD45RO, NKp44, CXCR6, CD57, NKG2C, CCR7, CD62L and CD27), influenza vaccines induced memory NK cells with the distinct feature of intracellular NKp46 expression. Indeed, surface NKp46 was internalized, and the dynamic increase in NKp46(intracellular)+CD56dim NK cells positively correlated with increased IFN-γ production to influenza virus restimulation after vaccination. In addition, anti-NKp46 antibodies blocked IFN-γ responses. These findings provide insights into a novel mechanism underlying vaccine-induced immunity and NK-related diseases, which may help to design persisting and universal vaccines in the future. 相似文献
994.
Wencai Pan Qingguang Yan Mingxin Qin Gui Jin Jian Sun Xu Ning Wei Zhuang Bin Peng Gen Li 《PloS one》2015,10(5)
Cerebral hemorrhage, a difficult issue in clinical practice, is often detected and studied with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). However, these expensive devices are not readily available in economically underdeveloped regions, and hence are unable to provide bedside and emergency on-site monitoring. The magnetic inductive phase shift (MIPS) is an emerging technology that may become a new tool to detect cerebral hemorrhage and to serve as an inexpensive partial substitute to medical imaging. In order to study a wider band of cerebral hemorrhage MIPS and to provide more useful information for measuring cerebral hemorrhage, we established a cerebral hemorrhage magnetic induction phase shift spectroscopy (MIPSS) detection system. Thirteen rabbits with five cerebral hemorrhage states were studied using a single coil-coil within a 1 MHz-200 MHz frequency range in linear sweep. A feature band (FB) with the highest detection sensitivity and the greatest stability was selected for further analysis and processing. In addition, a maximum conductivity cerebrospinal fluid (CSF) MRI was performed to verify and interpret the MIPSS result. The average phase shift change induced by a 3 ml injection of autologous blood under FB was -7.7503° ± 1.4204°, which was considerably larger than our previous work. Data analysis with a non-parametric statistical Friedman M test showed that in the FB, MIPSS could distinguish the five states of cerebral hemorrhage in rabbits, with a statistical significance of p<0.05. A B-F distribution profile was designed according to the MIPSS under FB that can provide instantaneous diagnostic information about the cerebral hemorrhage severity from a single set of measurements. The results illustrate that the MIPSS detection method is able to provide a new possibility for real-time monitoring and diagnosis of the severity of cerebral hemorrhage. 相似文献
995.
Xuefu Li Bomeng Zhong Weitian Han Ning Zhao Wei Liu Yu Sui Yawen Wang Yongping Lu Hong Wang Jianxin Li Miao Jiang 《PloS one》2015,10(2)
Distal arthrogryposes (DAs) are a group of disorders that mainly involve the distal parts of the limbs and at least ten different DAs have been described to date. DAs are mostly described as autosomal dominant disorders with variable expressivity and incomplete penetrance, but recently autosomal recessive pattern was reported in distal arthrogryposis type 5D. Mutations in the contractile genes are found in about 50% of all DA patients. Of these genes, mutations in the gene encoding myosin binding protein C slow MYBPC1 were recently identified in two families with distal arthrogryposis type 1B. Here, we described two large Chinese families with autosomal dominant distal arthrogryposis type 2(DA2) with incomplete penetrance and variable expressivity. Some unique overextension contractures of the lower limbs and some distinctive facial features were present in our DA2 pedigrees. We performed follow-up DNA sequencing after linkage mapping and first identified two novel MYBPC1 mutations (c.1075G>A [p.E359K] and c.956C>T [p.P319L]) responsible for these Chinese DA2 families of which one introduced by germline mosacism. Each mutation was found to cosegregate with the DA2 phenotype in each family but not in population controls. Both substitutions occur within C2 immunoglobulin domain, which together with C1 and the M motif constitute the binding site for the S2 subfragment of myosin. Our results expand the phenotypic spectrum of MYBPC1-related arthrogryposis multiplex congenita (AMC). We also proposed the possible molecular mechanisms that may underlie the pathogenesis of DA2 myopathy associated with these two substitutions in MYBPC1. 相似文献
996.
Feng Yang Moses M. Njire Jia Liu Tian Wu Bangxing Wang Tianzhou Liu Yuanyuan Cao Zhiyong Liu Junting Wan Zhengchao Tu Yaoju Tan Shouyong Tan Tianyu Zhang 《PloS one》2015,10(3)
In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn’t the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications. 相似文献
997.
Jian Wang Bo Xiang Hung Yu Lin Hongyu Liu Darren Freed Rakesh C. Arora Ganghong Tian 《PloS one》2015,10(3)
Objectives
Because the distribution volume and mechanism of extracellular and intravascular MR contrast media differ considerably, the enhancement pattern of chronic myocardial infarction with extracellular or intravascular media might also be different. This study aims to investigate the differences in MR enhancement patterns of chronic myocardial infarction between extracellular and intravascular contrast media.Materials and Methods
Twenty pigs with myocardial infarction underwent cine MRI, first pass perfusion MRI and delayed enhancement MRI with extracellular or intravascular media at four weeks after coronary occlusion. Myocardial blood flow (MBF) was determined with microsphere measurement. The infarction histopathological changes were evaluated by hematoxylin and eosin staining and Masson''s trichrome method.Results
Cine MRI revealed the reduced wall thickening in chronic infarction compared with normal myocardium. Moreover, significant wall thinning in chronic infarction was observed in cine MRI. Peak first-pass signal intensity didn’t significantly differ between chronic infarction and normal myocardium no matter what kinds of contrast media. At the following delayed enhancement phase, extracellular media-enhanced signal intensity was significantly higher in chronic infarction than in normal myocardium. Conversely, intravascular media-enhanced signal intensity was almost equivalent among chronic infarction and normal myocardium. At four weeks after infarction, MBF in chronic infarction approached to that in normal myocardium. Large thick-walled vessels were detected at peri-infarction zones. The cardiomyocytes were replaced by scar tissue consisting of dilated blood vessels and discrete fibers of collagen.Conclusions
Chronic infarction was characterized by the significantly reduced wall thickening and the definite wall thinning. First-pass myocardial perfusion defect was not detected in chronic infarction with two media due to the significantly recovered MBF and well-developed collateral vessels. Infarction remodeling enlarged the extracellular compartment, which was available for extracellular media but not accessible to intravascular media. Extracellular media identified chronic infarction as the hyper-enhancement; nonetheless, intravascular media didn’t provide delayed enhancement. 相似文献998.
Tian Chen Chen Wang Fang Wu Xuebang Zhang Han Yang Xia Deng Qiancheng He Wenfeng Li Gang Li 《PloS one》2015,10(3)
Background
P120 catenin (p120ctn), a regulator of cell adhesion, has previously been found in many malignancies, and suggested a role in invasion, metastasis and survival. The aim of this study was to investigate correlations between altered localization of p120ctn and clinical-pathological characteristics in esophageal squamous cell carcinoma (ESCC).Methods
Immunohistochemical staining for p120ctn was performed on tissue samples from 118 patients with ESCC. The expression of p120ctn was scored for intensity and cellular localization by Image-pro Plus 6.0. Correlations between immunohistochemical staining of p120ctn and pathological characteristics and clinical prognosis were determined using SPSS 18.0 software.Results
Membrane expression of p120ctn in ESCCs was lower than that in adjacentnormal esophageal epithelial tissues (P = 0.041), while overall cellular expression of p120ctn was not different between the two tissue types (P = 0.787). Furthermore, neither overall cellular expression nor localized membrane expression was associated with histological and clinical variables. The high ratio of membrane expression to overall cellular expression (M/C) of p120ctn was inversely associated with lymph node invasion (P = 0.001), tumor differentiation (P = 0.012) and advanced tumor stage (P = 0.005); however, it was poorly associated with T stage (P = 0.274). The high M/C ratio of p120ctn was inversely correlated with poor survival; the 5-year OS (overall survival) and the 5-year DFS (disease free survival) for the high M/C ratio group were significantly higher than those of the low M/C ratio group (41.0% vs. 6.7%, P = 0.000; 44.1% vs. 24.9%, P = 0.007). Both the M/C ratio of p120ctn and N status were independent variables for the prediction of overall survival (P = 0.007 and P = 0.027). The M/C of p120ctn predicted a 0.49-fold risk of ESCC death (p = 0.007, 95% CI 0.29–0.83).Conclusions
The reduced M/C ratio of p120ctn acted as an independent prognostic factor for ESCC patient survival and for the migration and invasive behavior of the disease. 相似文献999.
The aim of this study was to investigate the effects of choline supplementation on intramuscular fat (IMF) and lipid oxidation in IUGR pigs. Twelve normal body weight (NBW) and twelve intrauterine growth retardation (IUGR) newborn piglets were collected and distributed into 4 treatments (Normal: N, Normal+Choline: N+C, IUGR: I, and IUGR+Choline: I+C) with 6 piglets in each treatment. At 23 d of age, NBW and IUGR pigs were fed basal or choline supplemented diets. The results showed that the IUGR pigs had significantly lower (P<0.05) BW as compared with the NBW pigs at 23 d, 73 d, and 120 d of age, however, there was a slight decreased (P>0.05) in BW of IUGR pigs than the NBW pigs at 200 d. Compared with the NBW pigs, pH of meat longissimus dorsi muscle was significantly lower (P<0.05), and the meat color was improved in IUGR pigs. The malondialdehyde (MDA) levels were significantly decreased (P<0.05), while triglyceride (TG) and IMF contents were significantly higher (P<0.05) in the IUGR pigs than the NBW pigs. IUGR up-regulated the mRNA gene expression of fatty acid synthetase (FAS) and acetyl-CoA carboxylase (ACC). Dietary choline significantly increased (P<0.05) the BW at 120d of age, however, significantly decreased (P<0.05) the TG and IMF contents in both IUGR and NBW pigs. FAS and sterol regulatory element-binding proteins 1 (SREBP1) mRNA gene expressions were increased (P<0.05) while the muscle-carnitine palmityl transferase (M-CPT) and peroxisome proliferators-activated receptorγ (PPARγ) mRNA (P<0.05) gene expressions were decreased in the muscles of the IUGR pigs by choline supplementation. Furthermore, choline supplementation significantly increased (P<0.05) the MDA content as well as the O2•¯ scavenging activity in meat of IUGR pigs. The results suggested that IUGR pigs showed a permanent stunting effect on the growth performance, increased fat deposition and oxidative stress in muscles. However, dietary supplementation of choline improved the fat deposition via enhancing the lipogenesis and reducing the lipolysis. 相似文献
1000.