全文获取类型
收费全文 | 4685篇 |
免费 | 262篇 |
国内免费 | 4篇 |
出版年
2023年 | 10篇 |
2022年 | 46篇 |
2021年 | 82篇 |
2020年 | 51篇 |
2019年 | 77篇 |
2018年 | 125篇 |
2017年 | 77篇 |
2016年 | 153篇 |
2015年 | 209篇 |
2014年 | 248篇 |
2013年 | 329篇 |
2012年 | 371篇 |
2011年 | 322篇 |
2010年 | 225篇 |
2009年 | 223篇 |
2008年 | 277篇 |
2007年 | 239篇 |
2006年 | 209篇 |
2005年 | 226篇 |
2004年 | 204篇 |
2003年 | 227篇 |
2002年 | 175篇 |
2001年 | 81篇 |
2000年 | 96篇 |
1999年 | 67篇 |
1998年 | 49篇 |
1997年 | 41篇 |
1996年 | 39篇 |
1995年 | 34篇 |
1994年 | 17篇 |
1993年 | 24篇 |
1992年 | 29篇 |
1991年 | 23篇 |
1990年 | 26篇 |
1989年 | 32篇 |
1988年 | 17篇 |
1987年 | 11篇 |
1986年 | 16篇 |
1985年 | 17篇 |
1984年 | 17篇 |
1983年 | 23篇 |
1982年 | 26篇 |
1981年 | 22篇 |
1980年 | 19篇 |
1979年 | 13篇 |
1978年 | 10篇 |
1977年 | 12篇 |
1976年 | 19篇 |
1975年 | 12篇 |
1974年 | 11篇 |
排序方式: 共有4951条查询结果,搜索用时 31 毫秒
101.
Hye Jung Choi Jeoung-Yoon Seo Su Mi Hwang Yong-Ill Lee Yong Kee Jeong Ja-Young Moon Woo Hong Joo 《Biotechnology and Bioprocess Engineering》2013,18(5):1000-1007
Bacterial strains growing in river sediments were screened to identify an organic solvent-tolerant strain of Pseudomonas. Using this screen, Pseudomonas sp. BCNU 106 was isolated on the basis of its ability to grow on benzene, toluene, ethylbenzene, and three xylene isomers, o-, m- and p-xylene, as its sole carbon source. BCNU 106 was identified as a gram-negative, rod-shaped aerobic and mesophilic bacterium, which grew in liquid media containing high concentrations of organic solvents. 16S rDNA analysis classified BCNU 106 as a new member of the genus Pseudomonas. BCNU 106 was distinguishable from other Pseudomonas strains that are tolerant to organic solvents in that the isolate had the ability to utilize all three xylene isomers as well as benzene, toluene and ethylbenzene. The unique properties of the isolate such as solvent-tolerance and the ability to degrade xylene isomers may have important implications for the efficient treatment of solvent wastes. 相似文献
102.
103.
Nobuo N Noda Yuko Fujioka Takao Hanada Yoshinori Ohsumi Fuyuhiko Inagaki 《EMBO reports》2013,14(2):206-211
Atg12 is conjugated to Atg5 through enzymatic reactions similar to ubiquitination. The Atg12–Atg5 conjugate functions as an E3‐like enzyme to promote lipidation of Atg8, whereas lipidated Atg8 has essential roles in both autophagosome formation and selective cargo recognition during autophagy. However, the molecular role of Atg12 modification in these processes has remained elusive. Here, we report the crystal structure of the Atg12–Atg5 conjugate. In addition to the isopeptide linkage, Atg12 forms hydrophobic and hydrophilic interactions with Atg5, thereby fixing its position on Atg5. Structural comparison with unmodified Atg5 and mutational analyses showed that Atg12 modification neither induces a conformational change in Atg5 nor creates a functionally important architecture. Rather, Atg12 functions as a binding module for Atg3, the E2 enzyme for Atg8, thus endowing Atg5 with the ability to interact with Atg3 to facilitate Atg8 lipidation. 相似文献
104.
Changon Seo Yun-Hyeok Choi Jong Seog Ahn Joung Han Yim Hong Kum Lee 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):1133-1137
The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory natural products, the MeOH extract of the dried sample of the Antarctic lichen Umbilicaria antarctica was found to exhibit significant inhibitory effect, and the bioassay-guided fractionation and purification afforded three related lichen metabolites 1-3. Compounds 1-3 were identified as gyrophoric acid (1), lecanoric acid (2), and methyl orsellinate (3) mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 3.6 ± 0.04 μM, 31 ± 2.7 μM, and 277 ± 8.6 μM, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compound 1 suggested that the compound inhibited PTP1B activity in a non-competitive manner. 相似文献
105.
Chemical Conversion of Some Ribonucleosides into the Corresponding β-D-Arabinofuranosyl Derivatives1
Nobuo Sakairi Ichiro Hirao Yoshiaki Zama Yoshiharu Ishido 《Nucleosides, nucleotides & nucleic acids》2013,32(3):221-229
Abstract Five 3′,5′-di-O-acylribonucleosides were converted into the corresponding β-D-arabinofuranosyl derivatives through DMSO-oxidation followed by NaBH4-reduction and deacylation with NaOMe-MeOH. 相似文献
106.
Bit Na Seo Jung Min Ryu Seung Pil Yun Ji Hoon Jeon Su Shin Park Keon Bong Oh Jin-Ki Park Ho Jae Han 《Apoptosis : an international journal on programmed cell death》2013,18(7):811-824
Delphinidin, gallic acid, betulinic acid, and ursolic acid, which are bio-active ingredients in a variety of fruits, vegetables, and herbs, have potent antioxidant activity and various biological activities. However, it is not clear whether these bio-active ingredients can significantly contribute to the protection of embryonic stem (ES) cells from hypoxia-induced apoptosis. In the present study, hypoxia-induced ES cells apoptosis with time, which were abrogated by pretreatment with all ingredients. Hypoxia-induced ROS generation was blocked by pretreatment with all ingredients in a dose-dependent manner, with the maximum ROS scavenging effect observed for delphinidin. Hypoxia increased phosphorylation of JNK and NF-κB were blocked by pretreatment of delphinidin as well as NAC. Hypoxia decreased phosphorylation of Aktthr308 and ser473; these decreases were reversed by pretreatment with delphinidin or NAC. However, Akt inhibition did not affect NF-κB phosphorylation. Delphinidin attenuated the hypoxia-induced increase in Bax, cleaved caspase-9, cleaved caspase-3, and decrease in Bcl-2, which were diminished by pretreatment of Akt inhibitor. Hypoxia induced Bax translocation from the cytosol to mitochondria. Furthermore, hypoxia induced mitochondria membrane potential loss and cytochrome c release in cytosol, which were blocked by delphinidin pretreatment. Hypoxia induced cleavage of procaspase-9 and procaspase-3 which were blocked by delphinidin or SP600125, but Akt inhibitor abolished the protection effect of delphinidin. Moreover, inhibition of JNK and NF-κB abolished hypoxia-induced ES cell apoptosis and inhibition of Akt attenuated delphinidin-induced blockage of apoptosis. The results indicate that delphinidin can prevent hypoxia-induced apoptosis of ES cells through the inhibition of JNK and NF-κB phosphorylation, and restoration of Akt phosphorylation. 相似文献
107.
Keunhee Oh Myung Won Seo Ga Young Lee Ok-Jin Byoun Hye-Ryun Kang Sang-Heon Cho Dong-Sup Lee 《Respiratory research》2013,14(1):35
Background
Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens.Methods
We induced allergic asthma by ovalbumin sensitization and intranasal challenge in wild-type (WT) BALB/c and TG2-deficient mice. Broncheoalveolar lavage fluid cells and intracellular cytokine production were analyzed by flow cytometry. Interleukin (IL)-33 and TG2 expression in lung epithelial cells was detected by confocal microscopy.Results
Airway responsiveness was attenuated in TG2-deficient mice compared to that in the WT control. In addition, recruitment of eosinophils and Th2 and Th17 differentiation decreased in TG2-deficient mice. Treatment with cysteamine, a transglutaminase inhibitor, also reduced airway hypersensitivity, inflammatory cell recruitment, and T helper cell differentiation. TG2-deficient mice showed reduced IL-33 expression following induction of allergic asthma compared to those in the WT control.Conclusions
We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system. 相似文献108.
Jun Seo Goo Yo Na Kim Kyung Mi Choi In Sik Hwang Ji Eun Kim Young Ju Lee Moon Hwa Kwak Sun Bo Shim Seung Wan Jee Chul Joo Lim Je Kyung Seong Dae Youn Hwang 《Clinical proteomics》2013,10(1):10
Background
To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.Results
Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment.Conclusions
These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression. 相似文献109.
Miyako Kondoh Noritaka Ohga Kosuke Akiyama Yasuhiro Hida Nako Maishi Alam Mohammad Towfik Nobuo Inoue Masanobu Shindoh Kyoko Hida 《PloS one》2013,8(11)
There is much evidence that hypoxia in the tumor microenvironment enhances tumor progression. In an earlier study, we reported abnormal phenotypes of tumor-associated endothelial cells such as those resistant to chemotherapy and chromosomal instability. Here we investigated the role of hypoxia in the acquisition of chromosomal abnormalities in endothelial cells. Tumor-associated endothelial cells isolated from human tumor xenografts showed chromosomal abnormalities, >30% of which were aneuploidy. Aneuploidy of the tumor-associated endothelial cells was also shown by simultaneous in-situ hybridization for chromosome 17 and by immunohistochemistry with anti-CD31 antibody for endothelial staining. The aneuploid cells were surrounded by a pimonidazole-positive area, indicating hypoxia. Human microvascular endothelial cells expressed hypoxia-inducible factor 1 and vascular endothelial growth factor A in response to either hypoxia or hypoxia-reoxygenation, and in these conditions, they acquired aneuploidy in 7 days. Induction of aneuploidy was inhibited by either inhibition of vascular endothelial growth factor signaling with vascular endothelial growth factor receptor 2 inhibitor or by inhibition of reactive oxygen species by N-acetyl-L-cysteine. These results indicate that hypoxia induces chromosomal abnormalities in endothelial cells through the induction of reactive oxygen species and excess signaling of vascular endothelial growth factor in the tumor microenvironment. 相似文献
110.
Taeheon Lee Seoae Cho Kang Seok Seo Jongsoo Chang Heebal Kim Duhak Yoon 《BMB reports》2013,46(7):346-351
Although there have been many studies of native Korean cattle, Hanwoo, there have been no selective sweep studies in these animals. This study was performed to characterize genetic variation and identify selective signatures. We sequencedthe genomes of 12 cattle, and identified 15125420 SNPs, 1768114 INDELs, and 3445 CNVs. The SNPs, INDELs, and CNVs were similarly distributed throughout the genome, and highly variable regions were shown to contain the BoLA family and GPR180, which are related to adaptive immunity. We also identified the domestication footprints of the Hanwoo population by searching for selective sweep signatures, which revealed the RCN2 gene related to BPV resistance. The results of this study may contribute to genetic improvement of the Hanwoo population in Korea. [BMB Reports 2013; 46(7):346-351] 相似文献