全文获取类型
收费全文 | 1980篇 |
免费 | 151篇 |
国内免费 | 198篇 |
出版年
2024年 | 2篇 |
2023年 | 21篇 |
2022年 | 73篇 |
2021年 | 137篇 |
2020年 | 84篇 |
2019年 | 111篇 |
2018年 | 110篇 |
2017年 | 63篇 |
2016年 | 92篇 |
2015年 | 104篇 |
2014年 | 154篇 |
2013年 | 160篇 |
2012年 | 170篇 |
2011年 | 162篇 |
2010年 | 94篇 |
2009年 | 82篇 |
2008年 | 102篇 |
2007年 | 72篇 |
2006年 | 55篇 |
2005年 | 59篇 |
2004年 | 49篇 |
2003年 | 53篇 |
2002年 | 46篇 |
2001年 | 22篇 |
2000年 | 19篇 |
1999年 | 35篇 |
1998年 | 18篇 |
1997年 | 22篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 8篇 |
1992年 | 10篇 |
1991年 | 21篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1973年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有2329条查询结果,搜索用时 78 毫秒
61.
Ge-Ge Wang Guang Chen Hui Feng Jun Liu Yong-Jun Jiang Hong Shang Ya-Ming Cao 《Parasitology international》2013,62(1):24-31
Malaria infections display variation patterns of clinical course and outcome. Although CD4+CD25+Foxp3+ regulatory T (Treg) cells play an essential role in immune homeostasis, the immune regulatory roles involved in malaria infection remains to be elucidated. Herein, we compared the disparity in Treg cells response during the course of blood stage Plasmodium chabaudi chabaudi AS (P. c chabaudi AS) infection in DBA/2 and BALB/c mice. BALB/c mice initiated a Th1/Th2 profile respond to P. c chabaudi AS infection, but DBA/2 mice failed to control P. c chabaudi AS infection and almost of them died post-peak parasitemia. At the peak parasitemia, we found that higher proportion of Treg cells with elevated Foxp3 expression in DBA/2 than in BALB/c mice. We used anti-CD25 mAb to deplete Treg cells and found that the survival time and rate were prolonged in DBA/2 mice treated with anti-CD25 mAb. Treatment with anti-CD25 mAb in vivo led to enhanced pro-inflammation responses and Foxp3 expression decline on Treg cells. In contrast, after DBA/2 was treatment with anti-IL-10R mAb, IL-10R blockade in vivo caused excessive pro-inflammation responses and Foxp3 expression loss on CD4+CD25+ T cells. Earlier death was found in all of DBA/2 mice with anti-IL-10R mAb. It suggested that IL-2 and IL-10 signal involved in maintaining Foxp3 expression on Treg cells. In all, the moderate suppressive activity of Treg cells may facilitate resistance to P. c chabaudi AS infection. 相似文献
62.
Changjun Wang Lei Shang Yuhai Zhang Jiao Tian Baoxi Wang Xianjun Yang Lijun Sun Chunyan Du Xun Jiang Yongyong Xu 《PloS one》2013,8(10)
Aim
Functional constipation (FC) is one of the common diseases among children. The aim of this study was to investigate the health-related quality of life (HRQOL) in preschool children diagnosed with FC and the impact of the condition on affected families.Methods
In this cross-sectional, case-control study, 152 children aged 3–6 years with FC, 176 healthy children aged 3–6 years without FC, and their primary caregivers were selected. Chinese versions of the PedsQLTM 4.0 Generic Core Scale and the Family Impact Module (FIM) were used to assess childhood HRQOL and the impact of FC on family members, respectively. HRQOL scores were compared between children with FC and healthy children. In addition, a multiple step-wise regression with demographic variables of children and their caregivers, family economic status, duration and symptoms of FC, as independent variables, was used to determine factors that influenced HRQOL in children and had impacted caregivers.Results
Scores of physical, emotional, social and school functions, and summary scales were significantly lower in children with FC than in healthy children (p < 0.05). Physical, emotional, social, cognitive, and communication scores for caregivers, as well as daily activities and relationships for families of children with FC, were significantly lower than those of caregivers and families with healthy children (p < 0.05). Children’s ages, duration of FC, symptoms of FC, the child-caregiver relationship, family economic status, and caregiver education level emerged as the main factors influencing HRQOL in children, caregivers, and family members.Conclusions
FC had a significant impact on HRQOL of affected children and their caregivers, as well as their family functions. Social characteristics of children and caregivers, duration and symptoms of FC and family economic status significantly affected HRQOL of children and caregivers, as well as family functions of children with FC. 相似文献63.
Siu Wai Tsang Hongjie Zhang Chengyuan Lin Haitao Xiao Michael Wong Hongcai Shang Zhi-Jun Yang Aiping Lu Ken Kin-Lam Yung Zhaoxiang Bian 《PloS one》2013,8(12)
Pancreatic fibrosis, a prominent histopathological feature of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma, is essentially a dynamic process that leads to irreversible scarring of parenchymal tissues of the pancreas. Though the exact mechanisms of its initiation and development are poorly understood, recent studies suggested that the activation of pancreatic stellate cells (PSCs) plays a critical role in eliciting such active course of fibrogenesis. Anthraquinone compounds possess anti-inflammatory bioactivities whereas its natural derivative rhein has been shown to effectively reduce tissue edema and free-radical production in rat models of inflammatory conditions. Apart from its anti-inflammatory properties, rhein actually exerts strong anti-fibrotic effects in our current in-vivo and in-vitro experiments. In the mouse model of cerulein-induced CP, prolonged administration of rhein at 50 mg/kg/day significantly decreased immunoreactivities of the principal fibrotic activators alpha-smooth muscle actin (α-SMA) and transforming growth factor-beta (TGF-β) on pancreatic sections implicating the activation of PSCs, which is the central tread to fibrogenesis, was attenuated. Consequently, the overwhelmed deposition of extracellular matrix proteins fibronectin 1 (FN1) and type I collagen (COL I-α1) in exocrine parenchyma was found accordingly reduced. In addition, the expression levels of sonic hedgehog (SHH), which plays important roles in molecular modulation of various fibrotic processes, and its immediate effector GLI1 in pancreatic tissues were positively correlated to the degree of cerulein-induced fibrosis. Such up-regulation of SHH signaling was restrained in rhein-treated CP mice. In cultured PSCs, we demonstrated that the expression levels of TGF-β-stimulated fibrogenic markers including α-SMA, FN1 and COL I-α1 as well as SHH were all notably suppressed by the application of rhein at 10 μM. The present study firstly reported that rhein attenuates PSC activation and suppresses SHH/GLI1 signaling in pancreatic fibrosis. With strong anti-fibrotic effects provided, rhein can be a potential remedy for fibrotic and/or PSC-related pathologies in the pancreas. 相似文献
64.
Liang Zhao Ya Xing Wang Wei Zhang Jing Shang Zhang Chang Xi Chen Liang Xu Jost B. Jonas 《PloS one》2013,8(7)
Objective
To assess the prevalence of localized retinal nerve fiber layer defects (LRNFLD) and associated factors in adult Chinese.Methods
The population-based Beijing Eye Study 2011 included 3468 individuals (mean age: 64.6±9.8 years (range: 50–93 years)). The study participants underwent a detailed ophthalmological examination including spectral-domain optical coherence tomography (SpectralisR-OCT) assisted measurement of the RNFL. A LRNFLD was defined as a sector in which the RNFL contour line dipped into the red zone for a length of <180°.Results
Readable OCT images were available for 3242 (93.5%) subjects. LRNFLDs were detected in 640 eyes (9.9±0.4%) of 479 subjects (14.8±0.6%). In the age groups of 50–59 years, 60–69 years, 70–79 years, and 80+ years, the prevalence of LRNFLD per person increased from 9.9±0.9%, 11.6±1.0% and 20.6±1.4% to 33.0±3.2%, respectively. In multivariate analysis, prevalence of LRNFLDs was significantly associated with older age (P = 0.001; Odds Ratio (OR): 1.03; 95% Confidence Interval (CI): 1.01,1.05), myopic refractive error (P<0.001;OR:0.79;95%CI:0.74,0.85), larger beta zone of parapapillary atrophy (P<0.001; OR:1.34;95%CI:1.20,1.50), presence of glaucomatous optic neuropathy (P<0.001;OR:7.02;95%CI:3.87,12.7), presence of non-glaucomatous optic nerve damage (P = 0.001;OR:43.3;95%CI:8.24,227.1), and presence of diabetic retinopathy (P = 0.003;OR:2.79;95%CI:1.43,5.44).Conclusions
OCT-defined LRNFLDs were present in a prevalence of 14.8±0.6% in a population-based study sample of subjects aged 50+ years. Prevalence of LRNFLDs increased with higher age, myopic refractive error, and larger parapapillary beta zone. Major ocular diseases associated with LRNFLs were glaucoma, non-glaucomatous optic nerve damage and diabetic retinopathy. These data may be helpful for a semiautomatic assessment of the RNFL. 相似文献65.
Jianju Feng Dechun Jiang Huiying Shang Miao Dong Gaini Wang Xinyu He Changming Zhao Kangshan Mao 《PloS one》2013,8(8)
Background
Populus is an ecologically and economically important genus of trees, but distinguishing between wild species is relatively difficult due to extensive interspecific hybridization and introgression, and the high level of intraspecific morphological variation. The DNA barcoding approach is a potential solution to this problem.Methodology/Principal Findings
Here, we tested the discrimination power of five chloroplast barcodes and one nuclear barcode (ITS) among 95 trees that represent 21 Populus species from western China. Among all single barcode candidates, the discrimination power is highest for the nuclear ITS, progressively lower for chloroplast barcodes matK (M), trnG-psbK (G) and psbK-psbI (P), and trnH-psbA (H) and rbcL (R); the discrimination efficiency of the nuclear ITS (I) is also higher than any two-, three-, or even the five-locus combination of chloroplast barcodes. Among the five combinations of a single chloroplast barcode plus the nuclear ITS, H+I and P+I differentiated the highest and lowest portion of species, respectively. The highest discrimination rate for the barcodes or barcode combinations examined here is 55.0% (H+I), and usually discrimination failures occurred among species from sympatric or parapatric areas.Conclusions/Significance
In this case study, we showed that when discriminating Populus species from western China, the nuclear ITS region represents a more promising barcode than any maternally inherited chloroplast region or combination of chloroplast regions. Meanwhile, combining the ITS region with chloroplast regions may improve the barcoding success rate and assist in detecting recent interspecific hybridizations. Failure to discriminate among several groups of Populus species from sympatric or parapatric areas may have been the result of incomplete lineage sorting, frequent interspecific hybridizations and introgressions. We agree with a previous proposal for constructing a tiered barcoding system in plants, especially for taxonomic groups that have complex evolutionary histories (e.g. Populus). 相似文献66.
Ying-Xia Cui Xin-Yi Xia Yang Zhou Lin Gao Xue-Jun Shang Tong Ni Wei-Ping Wang Xiao-Buo Fan Hong-Lin Yin Shao-Jun Jiang Bing Yao Yu-An Hu Gang Wang Xiao-Jun Li 《PloS one》2013,8(11)
Objective
Dyschromatosis universalis hereditaria (DUH) is a rare heterogeneous pigmentary genodermatosis, which was first described in 1933. The genetic cause has recently been discovered by the discovery of mutations in ABCB6. Here we investigated a Chinese family with typical features of autosomal dominant DUH and 3 unrelated patients with sporadic DUH.Methods
Skin tissues were obtained from the proband, of this family and the 3 sporadic patients. Histopathological examination and immunohistochemical analysis of ABCB6 were performed. Peripheral blood DNA samples were obtained from 21 affected, 14 unaffected, 11 spouses in the family and the 3 sporadic patients. A genome-wide linkage scan for the family was carried out to localize the causative gene. Exome sequencing was performed from 3 affected and 1 unaffected in the family. Sanger sequencing of ABCB6 was further used to identify the causative gene for all samples obtained from available family members, the 3 sporadic patients and a panel of 455 ethnically-matched normal Chinese individuals.Results
Histopathological analysis showed melanocytes in normal control’s skin tissue and the hyperpigmented area contained more melanized, mature melanosomes than those within the hypopigmented areas. Empty immature melanosomes were found in the hypopigmented melanocytes. Parametric multipoint linkage analysis produced a HLOD score of 4.68, with markers on chromosome 2q35-q37.2. A missense mutation (c.1663 C>A, p.Gln555Lys) in ABCB6 was identified in this family by exome and Sanger sequencing. The mutation perfectly cosegregated with the skin phenotype. An additional mutation (g.776 delC, c.459 delC) in ABCB6 was found in an unrelated sporadic patient. No mutation in ABCB6 was discovered in the other two sporadic patients. Neither of the two mutations was present in the 455 controls. Melanocytes showed positive immunoreactivity to ABCB6.Conclusion
Our data add new variants to the repertoire of ABCB6 mutations with DUH. 相似文献67.
Fangyou Yu Ying Liu Yuanyuan Xu Yongpeng Shang Danping Lou Zhiqiang Qin Chris Parsons Wu Zhou Xiaoying Huang Yuping Li Longhua Hu Liangxing Wang 《PloS one》2013,8(12)
Panton-Valentine leukocidin (PVL; gene designation lukF/S-PV) is likely an important virulence factor for Staphylococcus aureus (S. aureus), as qualitative expression of the protein correlates with severity for specific clinical presentations, including skin and soft tissue infections (SSTIs). Development of genetic approaches for risk-assessment of patients with S. aureus infections may prove clinically useful, and whether lukF/S-PV gene expression correlates with specific clinical presentations for S. aureus has been largely unexplored. In the present study, we quantified lukS-PV mRNA among 96 S. aureus isolates to determine whether expression levels correlated with specific clinical presentations in adults and children. Expression level of lukS-PV mRNA among isolates from skin and soft tissue infections (SSTIs) was significantly greater than among isolates from blood stream infection (BSIs), and expression level of lukS-PV mRNA among BSI isolates from children was significantly greater than for BSI isolates among adults. Moreover, expression level of lukS-PV mRNA among community-acquired (CA) isolates was significantly greater than for hospital-acquired (HA) isolates. These data justify additional studies to determine the potential clinical utility for lukS-PV mRNA quantification as a predictive tool for severity of S. aureus infection. 相似文献
68.
通过对甘农3号、甘农5号和游客紫花苜蓿多元杂交后代选育的36个株系及其亲本的生长、产量、品质等相关指标的测定,采用灰色关联度理论,构造综合评价模型进行供试材料综合评价,筛选出速生12#、速生11#株系为最理想的优良株系,生长高度分别为105.44cm、105.42cm;生长速度分别为1.74cm/d、1.68cm/d;茎叶比分别为0.30、0.35;分枝数分别为23、17;鲜草产量分别为39.99 t/hm2、35.13 t/hm2;粗蛋白含量分别为19.95%、23.89%;相对饲用价值为153.15%、157.02%。多叶2#、速生5#、速生20#、速生21#等4个株系为较理想的优良株系。 相似文献
69.
Yun-Song Wang Rong Huang Yan Li Wen-Bin Shang Fei Chen Hong-Bin Zhang Jing-Hua Yang 《Phytochemistry letters》2013,6(1):26-30
A pair of novel tetrahydrobenzofuran derivatives with a unique C18 carbon skeleton, panamonon A (1) and B (2), was isolated from the leaves and twigs of Litsea panamonja (Nees) Hook. f. These new compounds contain an unprecedented C18 carbon skeleton consisting of a characteristic tetrahydrobenzofuran-2,5(3H,6H)-dione core with a biosynthetically extended geranyl side chain, designated as “panamonane”.Highlights? A pair of novel tetrahydrobenzofuran derivatives with a unique C18 carbon skeleton was isolated. ? The new compounds possess an unprecedented C18 carbon skeleton and are designated as “panamonane”. ? They are featured with a tetrahydrobenzofuran-2,5(3H,6H)-dione moiety and a geranyl side chain. ? The plausible biosynthetic pathways of them were discussed. 相似文献
70.
Ling Zhang Dandan Zhang Baowen Yu Shangbo Wang Yanlin Liu Jian Wang Xin Li Xiaoyun Shang Hongyuan Li 《PloS one》2013,8(3)