全文获取类型
收费全文 | 83317篇 |
免费 | 6898篇 |
国内免费 | 5113篇 |
专业分类
95328篇 |
出版年
2024年 | 148篇 |
2023年 | 938篇 |
2022年 | 2173篇 |
2021年 | 3763篇 |
2020年 | 2432篇 |
2019年 | 2985篇 |
2018年 | 3041篇 |
2017年 | 2145篇 |
2016年 | 3076篇 |
2015年 | 4858篇 |
2014年 | 5611篇 |
2013年 | 6247篇 |
2012年 | 7297篇 |
2011年 | 6730篇 |
2010年 | 4040篇 |
2009年 | 3593篇 |
2008年 | 4355篇 |
2007年 | 3879篇 |
2006年 | 3364篇 |
2005年 | 2856篇 |
2004年 | 2445篇 |
2003年 | 2124篇 |
2002年 | 1883篇 |
2001年 | 1649篇 |
2000年 | 1625篇 |
1999年 | 1511篇 |
1998年 | 905篇 |
1997年 | 838篇 |
1996年 | 845篇 |
1995年 | 768篇 |
1994年 | 715篇 |
1993年 | 552篇 |
1992年 | 838篇 |
1991年 | 684篇 |
1990年 | 623篇 |
1989年 | 550篇 |
1988年 | 430篇 |
1987年 | 370篇 |
1986年 | 348篇 |
1985年 | 312篇 |
1984年 | 222篇 |
1983年 | 208篇 |
1982年 | 117篇 |
1981年 | 127篇 |
1980年 | 89篇 |
1979年 | 152篇 |
1978年 | 87篇 |
1977年 | 97篇 |
1975年 | 112篇 |
1974年 | 116篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
811.
Background
Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages.Methodology/Principal Findings
The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16+ subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16+ monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16− monocytes/macrophages. Furthermore, peripheral blood CD16+ monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores.Conclusions
These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease. 相似文献812.
Chen CY Tsai YL Kao CL Lee SD Wu MC Mallikarjuna K Liao YH Ivy JL Kuo CH 《The Chinese journal of physiology》2010,53(1):62-71
The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes. 相似文献
813.
A mathematical model has been presented for a high speed liquid jet penetration into soft solid by a needle-free injection system. The model consists of a cylindrical column formed by the initial jet penetration and an expansion sphere due to continuous deposition of the liquid. By solving the equations of energy conservation and volume conservation, the penetration depth and the radius of the expansion sphere can be predicted. As an example, the calculation results were presented for a typical needle-free injection system into which a silicon rubber was injected into. The calculation results were compared with the experimental results. 相似文献
814.
A major QTL for resistance to Gibberella stalk rot in maize 总被引:1,自引:0,他引:1
Qin Yang Guangming Yin Yanling Guo Dongfeng Zhang Shaojiang Chen Mingliang Xu 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(4):673-687
Fusarium graminearum Schwabe, the conidial form of Gibberella zeae, is the causal fungal pathogen responsible for Gibberella stalk rot of maize. Using a BC1F1 backcross mapping population derived from a cross between ‘1145’ (donor parent, completely resistant) and ‘Y331’ (recurrent
parent, highly susceptible), two quantitative trait loci (QTLs), qRfg1 and qRfg2, conferring resistance to Gibberella stalk rot have been detected. The major QTL qRfg1 was further confirmed in the double haploid, F2, BC2F1, and BC3F1 populations. Within a qRfg1 confidence interval, single/low-copy bacterial artificial chromosome sequences, anchored expressed sequence tags, and insertion/deletion
polymorphisms, were exploited to develop 59 markers to saturate the qRfg1 region. A step by step narrowing-down strategy was adopted to pursue fine mapping of the qRfg1 locus. Recombinants within the qRfg1 region, screened from each backcross generation, were backcrossed to ‘Y331’ to produce the next backcross progenies. These
progenies were individually genotyped and evaluated for resistance to Gibberella stalk rot. Significant (or no significant) difference in resistance reactions between homozygous and heterozygous genotypes
in backcross progeny suggested presence (or absence) of qRfg1 in ‘1145’ donor fragments. The phenotypes were compared to sizes of donor fragments among recombinants to delimit the qRfg1 region. Sequential fine mapping of BC4F1 to BC6F1 generations enabled us to progressively refine the qRfg1 locus to a ~500-kb interval flanked by the markers SSR334 and SSR58. Meanwhile, resistance of qRfg1 to Gibberella stalk rot was also investigated in BC3F1 to BC6F1 generations. Once introgressed into the ‘Y331’ genome, the qRfg1 locus could steadily enhance the frequency of resistant plants by 32–43%. Hence, the qRfg1 locus was capable of improving maize resistance to Gibberella stalk rot. 相似文献
815.
Ju-Hong Zhang Li-Wen Sun Lin-Lin Liu Jie Lian Shao-Li An Xu Wang Jing Zhang Jun-Ling Jin Shan-Yu Li Jing-Hui Xi 《Plant Molecular Biology Reporter》2010,28(2):324-333
In this study, comparative proteomics was used to investigate the interaction of Spodoptera exigua and Arabidopsis thaliana. By using 2-D electrophoresis of differentially expressed proteins, combined with high-throughput matrix-assisted laser desorption/ionization
time of flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF/TOF MS, the changes in the abundance of proteins induced by
insect feeding were studied in A. thaliana. More than 1,100 protein spots were reproducibly detected on each gel. The intensities of 30 protein spots in particular
changed significantly, showing differences in volume of at least twofold. Among these, 17 protein spots were upregulated,
and 13 were downregulated following an 8-h insect feeding period. Nineteen insect-feeding-responsive proteins were identified,
all of which were involved in metabolic regulation, binding functions or cofactor requirement of protein, cell rescue, and
defense and virulence, as assessed by Munich Information Center for Protein Sequences function category. About 50% of these
were involved in metabolism, including transketolase, S-adenosylmethionine synthase 3, 2,3-biphosphoglycerate-independent phosphoglycerate mutase, beta-ureidopropionase, GDP-d-mannose 3′,5′-epimerase, and fatty acid synthase. The identification of insect-feeding-responsive proteins on Arabidopsis provides not only new insights into insect stress but also a good start for further investigation of their functions. Understanding
how the plant responses to insects in the proteomic level will provide tools for a better management of insect pest in the
field. 相似文献
816.
SuiKang Wang YouHuang Bai ChenJia Shen YunRong Wu SaiNa Zhang DeAn Jiang Tom J. Guilfoyle Ming Chen YanHua Qi 《Functional & integrative genomics》2010,10(4):533-546
Sorghum, a C4 model plant, has been studied to develop an understanding of the molecular mechanism of resistance to stress.
The auxin-response genes, auxin/indole-3-acetic acid (Aux/IAA), auxin-response factor (ARF), Gretchen Hagen3 (GH3), small
auxin-up RNAs, and lateral organ boundaries (LBD), are involved in growth/development and stress/defense responses in Arabidopsis and rice, but they have not been studied in sorghum. In the present paper, the chromosome distribution, gene duplication,
promoters, intron/exon, and phylogenic relationships of Aux/IAA, ARF, GH3, and LBD genes in sorghum are presented. Furthermore,
real-time PCR analysis demonstrated these genes are differently expressed in leaf/root of sorghum and indicated the expression
profile of these gene families under IAA, brassinosteroid (BR), salt, and drought treatments. The SbGH3 and SbLBD genes, expressed
in low level under natural condition, were highly induced by salt and drought stress consistent with their products being
involved in both abiotic stresses. Three genes, SbIAA1, SbGH3-13, and SbLBD32, were highly induced under all the four treatments,
IAA, BR, salt, and drought. The analysis provided new evidence for role of auxin in stress response, implied there are cross
talk between auxin, BR and abiotic stress signaling pathways. 相似文献
817.
表达SLTEC保护性抗原的重组猪霍乱沙门氏菌C500株的构建及生物学特性 总被引:1,自引:0,他引:1
摘要:【目的】 利用平衡致死系统构建表达产类志贺氏毒素大肠杆菌(Shiga-like toxin Escherichia coli , SLTEC)保护性抗原的减毒猪霍乱沙门氏菌。【方法】 构建表达SLT-IIeB-FedF的重组质粒 ,再将其电转入终宿主菌减毒猪霍乱沙门氏菌ΔasdC500株中构建成口服活疫苗株 ,经聚丙烯酰胺凝胶电泳检测SLT-IIeB-FedF融合蛋白的表达情况,并观察重组菌体外培养的稳定性。【结果】 利用宿主-载体平衡致死系统构建了表达SLTEC保护性抗原的重组减毒猪霍乱沙门氏菌 相似文献
818.
Available resources could influence the trade-offs among different reproductive components in plants. Here, we created three nutrient levels to test the nutrient effects on trade-offs among sexual reproduction, clonal propagation and vegetative growth in a monoecious clonal herb Sagittaria pygmaea. The results of this study showed that the plant exhibited different trade-off patterns among different nutrient levels. When the nutrient level was low, there were weak trade-offs between sexual reproduction and vegetative growth and between clonal propagation and vegetative growth; when the nutrient level was moderate, we found a strong trade-off between sexual reproduction and clonal propagation; but when the nutrient level was high, we found no trade-offs among these three different reproductive components. These results indicated that the plant could adjust its trade-off patterns to fit the nutrient variation and suggested that trade-offs are unlikely to constrain the evolution of reproductive strategy in this species. 相似文献
819.
组蛋白H3第79位赖氨酸甲基化(H3K79me)修饰有单甲基、双甲基及三甲基3种形式,是常染色质的标志.然而,对于组蛋白H3K79三种甲基化各自在基因转录、DNA损伤修复中所起的作用尚不十分清楚.本研究以8-氯腺苷(8-Cl-Ado)为DNA双链断裂(DNA double-stranded breaks,DSB)诱导剂,采用Western 印迹,在人肺癌细胞H1299检测出了DNA修复分子NBS1、细胞周期检验点相关分子p21,并发现H3K79me1、H3K79me2和H3K79me3三种甲基化修饰的组蛋白明显增加;染色质免疫共沉淀结合实时定量PCR实验显示,只H3K79me2与DNA损伤检验点分子p21、DNA修复分子NBS1的启动子区域相结合,说明H3K79双甲基化修饰与这些基因的转录激活有关.结果提示,在8-氯腺苷引起 DSB时,是H3K79me2、而不是H3K79me1和H3K79me3参与NBS1和p21基因转录激活时的染色质重塑.8-氯腺苷诱导H3K79双甲基化增强、促进H3K79me2所在染色质区域的NBS1和p21基因转录激活可能是8-Cl-Ado抑制肿瘤细胞生长作用机制之一. 相似文献
820.