全文获取类型
收费全文 | 15770篇 |
免费 | 1053篇 |
国内免费 | 8篇 |
专业分类
16831篇 |
出版年
2024年 | 24篇 |
2023年 | 61篇 |
2022年 | 206篇 |
2021年 | 309篇 |
2020年 | 204篇 |
2019年 | 284篇 |
2018年 | 407篇 |
2017年 | 348篇 |
2016年 | 572篇 |
2015年 | 862篇 |
2014年 | 986篇 |
2013年 | 1064篇 |
2012年 | 1440篇 |
2011年 | 1332篇 |
2010年 | 877篇 |
2009年 | 680篇 |
2008年 | 1007篇 |
2007年 | 891篇 |
2006年 | 814篇 |
2005年 | 747篇 |
2004年 | 731篇 |
2003年 | 576篇 |
2002年 | 475篇 |
2001年 | 380篇 |
2000年 | 351篇 |
1999年 | 245篇 |
1998年 | 109篇 |
1997年 | 91篇 |
1996年 | 63篇 |
1995年 | 63篇 |
1994年 | 50篇 |
1993年 | 42篇 |
1992年 | 88篇 |
1991年 | 63篇 |
1990年 | 45篇 |
1989年 | 52篇 |
1988年 | 29篇 |
1987年 | 34篇 |
1986年 | 24篇 |
1985年 | 25篇 |
1984年 | 15篇 |
1983年 | 18篇 |
1982年 | 14篇 |
1981年 | 12篇 |
1980年 | 13篇 |
1979年 | 10篇 |
1978年 | 17篇 |
1975年 | 13篇 |
1974年 | 11篇 |
1970年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Mao S Lee SJ Hwangbo H Kim YW Park KH Cha GS Park RD Kim KY 《Current microbiology》2006,53(5):358-364
A new antagonistic Burkholderia strain, designated MP-1 and producing antifungal activities against various filamentous plant pathogenic fungi, was isolated
from the rhizoshere in the Naju area. Cultural characteristic studies strongly suggested that this strain belongs to the genus
Burkholderia. The nucleotide sequence of the 16S rRNA gene (1491 pb) of strain MP-1 exhibited close similarity (99% to 100%) with other
Burkholderia 16S rRNA genes. Extraction of fermentation broth of Burkholderia sp. MP-1 and various separations and purification steps led to isolation of four pure active molecules. The chemical structure
of these four compounds—named phenylacetic acid, hydrocinnamic acid, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetate
methyl ester—was established on the basis on their gas chromatography–electron impact–mass spectrometry (GC-EI-MS) and trimethylsilation
GC-EI-MS data. The four isolated compounds inhibited filamentous fungal growth on potato dextrose agar medium supplemented
with 100 mg/L of phenylacetic acid, hydrocinnamic acid, 4-hydroxyphenylacetic acid and 4-hydroxyphenylacetate methyl ester
individually. 相似文献
92.
Dah Ihm Kim Ki Hoon Lee Ji Young Oh Jun Sung Kim Ho Jae Han 《Cellular and molecular neurobiology》2017,37(6):955-968
Mitochondria as dynamic organelles undergo morphological changes through the processes of fission and fusion which are major factors regulating their functions. A disruption in the balance of mitochondrial dynamics induces functional disorders in mitochondria such as failed energy production and the generation of reactive oxygen species, which are closely related to pathophysiological changes associated with Alzheimer’s disease (AD). Recent studies have demonstrated a relationship between abnormalities in mitochondrial dynamics and impaired mitochondrial function, clarifying the effects of morphofunctional aberrations which promote neuronal cell death in AD. Several possible signaling pathways have been suggested for a better understanding of the mechanism behind the key molecules regulating mitochondrial morphologies. However, the exact machinery involved in mitochondrial dynamics still has yet to be elucidated. This paper reviews the current knowledge on signaling mechanisms involved in mitochondrial dynamics and the significance of mitochondrial dynamics in controlling associated functions in neurodegenerative diseases, particularly in AD. 相似文献
93.
Gwang Hoon Kim Jun Bo Shim Tatyana A. Klochkova John A. West Giuseppe C. Zuccarello 《Journal of phycology》2008,44(6):1519-1528
A comparison of the proteome of eight genetically well‐characterized isolates of the Bostrychia radicans (Mont.) Mont./B. moritziana (Sond. ex Kütz.) J. Agardh species complex was undertaken to establish if genetic relationships among them can be determined using proteome data. Genetic distances were calculated on the basis of common and distinct spots in two‐dimensional gel electrophoresis (2‐DE). Proteomes of the male and female plants of each population were compared to analyze the range of genetic difference within an isolate. Haploid male and female plants of the same species had 3.7%–7.1% sex‐specific proteins. The degree of similarity of the proteome was consistent with previous DNA sequence data and sexual compatibility studies between the isolates. Two sexually compatible isolates from Venezuela showed a pair‐wise distance ranging from 0.14 to 0.21. The isolates from Mexico and Venezuela, which were partially compatible, showed a maximum pair‐wise distance of 0.26. A high level of genetic difference was found among isolates that were sexually incompatible. The isolate from Brazil was reproductively isolated from the Mexico and Venezuela isolates and showed a maximum pair‐wise distance of 0.65 and 0.58, respectively. Comparative proteomics may be helpful for studying genetic distances among algal samples, if intraisolate variation (gene expression) can be minimized or tested. 相似文献
94.
Jongchan Lee Junhyeok Choi Jeongwook Lee Yongmin Cho In-Jeong Kang Sang-Wook Han 《The Plant Pathology Journal》2022,38(4):410
Erwinia amylovora, the causal agent of fire-blight disease in apple and pear trees, was first isolated in South Korea in 2015. Although numerous studies, including omics analyses, have been conducted on other strains of E. amylovora, studies on South Korean isolates remain limited. In this study, we conducted a comparative proteomic analysis of the strain TS3128, cultured in three media representing different growth conditions. Proteins related to virulence, type III secretion system, and amylovoran production, were more abundant under minimal conditions than in rich conditions. Additionally, various proteins associated with energy production, carbohydrate metabolism, cell wall/membrane/envelope biogenesis, and ion uptake were identified under minimal conditions. The strain TS3128 expresses these proteins to survive in harsh environments. These findings contribute to understanding the cellular mechanisms driving its adaptations to different environmental conditions and provide proteome profiles as reference for future studies on the virulence and adaptation mechanisms of South Korean strains. 相似文献
95.
Hyunsup Kim Dongmin Kim Hyemin Choi Gwangsu Shin Joon-Kyu Lee 《The Journal of biological chemistry》2023,299(1)
The MRE11–RAD50–NBS1 (MRN) complex plays essential roles in the cellular response to DNA double-strand breaks (DSBs), which are the most cytotoxic DNA lesions, and is a target of various modifications and controls. Recently, lysine 48-linked ubiquitination of NBS1, resulting in premature disassembly of the MRN complex from DSB sites, was observed in cells lacking RECQL4 helicase activity. However, the role and control of this ubiquitination during the DSB response in cells with intact RECQL4 remain unknown. Here, we showed that USP2 counteracts this ubiquitination and stabilizes the MRN complex during the DSB response. By screening deubiquitinases that increase the stability of the MRN complex in RECQL4-deficient cells, USP2 was identified as a new deubiquitinase that acts at DSB sites to counteract NBS1 ubiquitination. We determined that USP2 is recruited to DSB sites in a manner dependent on ATM, a major checkpoint kinase against DSBs, and stably interacts with NBS1 and RECQL4 in immunoprecipitation experiments. Phosphorylation of two critical residues in the N terminus of USP2 by ATM is required for its recruitment to DSBs and its interaction with RECQL4. While inactivation of USP2 alone does not substantially influence the DSB response, we found that inactivation of USP2 and USP28, another deubiquitinase influencing NBS1 ubiquitination, results in premature disassembly of the MRN complex from DSB sites as well as defects in ATM activation and homologous recombination repair abilities. These results suggest that deubiquitinases counteracting NBS1 ubiquitination are essential for the stable maintenance of the MRN complex and proper cellular response to DSBs. 相似文献
96.
It has been recently that particulate matter (PM) exposure increases the risk and exacerbation of allergic asthma. However, the underlying mechanisms and factors associated with increased allergic responses remain elusive. We evaluated IL‐23 and IL‐23R (receptor) expression, as well as changes in the asthmatic phenotype in mice administered PM and a low dose of house dust mite (HDM). Next, changes in the phenotype and immune responses were evaluated after intranasal administration of anti‐IL‐23 antibody during co‐exposure to PM and low‐dose HDM. We also performed in vitro experiments to investigate the effect of IL‐23. IL‐23 expression was significantly increased in Epcam+CD45− and CD11c+ cells, while that of IL‐23R was increased in Epcam+CD45− cells only in mice administered PM and low‐dose HDM. Administration of anti‐IL‐23 antibody led to decreased airway hyperresponsiveness, eosinophils, and activation of dendritic cells, reduced populations of Th2 Th17, ILC2, the level of IL‐33 and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Inhibition of IL‐23 in PM and low‐dose HDM stimulated airway epithelial cell line resulted in decreased IL‐33, GM‐CSF and affected ILC2 and the activation of BMDCs. PM augmented the phenotypes and immunologic responses of asthma even at low doses of HDM. Interestingly, IL‐23 affected immunological changes in airway epithelial cells. 相似文献
97.
Root segments from seedlings of Panax ginseng produced adventitious roots directly when cultured on 1/2 MS solid medium lacking NH4NO3 and containing 3.0 mg l−1 IBA. Using this adventitious root formation, we developed rapid and efficient transgenic root formation directly from adventitious
root segments in P. ginseng. Root segments were co-cultivated with Agrobacterium tumefaciens (GV3101) caring β-glucuronidase (GUS) gene. Putative transgenic adventitious roots were formed directly from root segments on medium with 400 mg l−1 cefotaxime and 50 mg l−1 kanamycin. Kanamycin resistant adventitious roots were selected and proliferated as individual lines by subculturing on medium
with 300 mg l−1 cefotaxime and 50 mg l−1 kanamycin at two weeks subculture interval. Frequency of transient and stable expression of GUS gene was enhanced by acetosyringon (50 mg l−1) treatment. Integration of transgene into the plants was confirmed by the X-gluc reaction, PCR and Southern analysis. Production
of transgenic plants was achieved via somatic embryogenesis from the embryogenic callus derived from independent lines of
adventitious roots. The protocol for rapid induction of transgenic adventitious roots directly from adventitious roots can
be applied for a new Agrobacterium tumefaciens-mediated genetic transformation protocol in P. ginseng. 相似文献
98.
99.
Pauls E Shpiro N Peggie M Young ER Sorcek RJ Tan L Choi HG Cohen P 《The Journal of biological chemistry》2012,287(23):19216-19228
Plasmacytoid dendritic cells (pDCs) are characterized by their ability to produce high levels of type 1 interferons in response to ligands that activate TLR7 and TLR9, but the signaling pathways required for IFN production are incompletely understood. Here we exploit the human pDC cell line Gen2.2 and improved pharmacological inhibitors of protein kinases to address this issue. We demonstrate that ligands that activate TLR7 and TLR9 require the TAK1-IKKβ signaling pathway to induce the production of IFNβ via a pathway that is independent of the degradation of IκBα. We also show that IKKβ activity, as well as the subsequent IFNβ-stimulated activation of the JAK-STAT1/2 signaling pathway, are essential for the production of IFNα by TLR9 ligands. We further show that TLR7 ligands CL097 and R848 fail to produce significant amounts of IFNα because the activation of IKKβ is not sustained for a sufficient length of time. The TLR7/9-stimulated production of type 1 IFNs is inhibited by much lower concentrations of IKKβ inhibitors than those needed to suppress the production of NFκB-dependent proinflammatory cytokines, such as IL-6, suggesting that drugs that inhibit IKKβ may have a potential for the treatment of forms of lupus that are driven by self-RNA and self-DNA-induced activation of TLR7 and TLR9, respectively. 相似文献
100.
Byoung-Shik Shim Jung-ah Choi Ho-Hyun Song Sung-Moo Park In Su Cheon Ji-Eun Jang Sun Je Woo Chung Hwan Cho Min-Suk Song Hyemi Kim Kyung Joo Song Jae Myun Lee Suhng Wook Kim Dae Sub Song Young Ki Choi Jae-Ouk Kim Huan Huu Nguyen Dong Wook Kim Young Yil Bahk Cheol-Heui Yun Man Ki Song 《Journal of microbiology (Seoul, Korea)》2013,51(1):130-135
Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics. 相似文献