全文获取类型
收费全文 | 3404篇 |
免费 | 231篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 8篇 |
2022年 | 37篇 |
2021年 | 60篇 |
2020年 | 39篇 |
2019年 | 45篇 |
2018年 | 91篇 |
2017年 | 64篇 |
2016年 | 122篇 |
2015年 | 169篇 |
2014年 | 222篇 |
2013年 | 249篇 |
2012年 | 304篇 |
2011年 | 281篇 |
2010年 | 179篇 |
2009年 | 164篇 |
2008年 | 210篇 |
2007年 | 202篇 |
2006年 | 194篇 |
2005年 | 148篇 |
2004年 | 193篇 |
2003年 | 115篇 |
2002年 | 109篇 |
2001年 | 112篇 |
2000年 | 71篇 |
1999年 | 64篇 |
1998年 | 16篇 |
1997年 | 21篇 |
1996年 | 12篇 |
1995年 | 11篇 |
1994年 | 5篇 |
1993年 | 9篇 |
1992年 | 17篇 |
1991年 | 17篇 |
1990年 | 21篇 |
1989年 | 15篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有3636条查询结果,搜索用时 484 毫秒
211.
Daria A. Gaykalova Rajita Vatapalli Yingying Wei Hua-Ling Tsai Hao Wang Chi Zhang Patrick T. Hennessey Theresa Guo Marietta Tan Ryan Li Julie Ahn Zubair Khan William H. Westra Justin A. Bishop David Zaboli Wayne M. Koch Tanbir Khan Michael F. Ochs Joseph A. Califano 《PloS one》2015,10(11)
Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC. 相似文献
212.
213.
Long Jin Hyung-Gwan Lee Hyun-Joon La So-Ra Ko Chi-Yong Ahn Hee-Mock Oh 《Antonie van Leeuwenhoek》2014,106(2):319-323
A Gram-negative, aerobic, non-motile, and rod-shaped bacterium, designated strain DS48-5-3T, was isolated from a 48 m sediment sample taken from Daechung Reservoir, Republic of Korea. Comparative 16S rRNA gene sequence studies showed a clear affiliation of this strain to the Bacteroidetes, notably most closely related to Ferruginibacter alkalilentus HU1-GD23T, Ferruginibacter lapsinanis HU1-HG42T and Ferruginibacter yonginensis HME8442T, showing 16S rRNA gene sequence similarities to the type strains of these species of 95.2–96.4 % similarity. The predominant ubiquinone was identified as MK-7. The major fatty acids were identified as iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G. The G+C content of the genomic DNA of strain DS48-5-3T was determined to be 37.2 %. On the basis of polyphasic evidence, it is proposed that strain DS48-5-3T should belong to a novel species, for which the name Ferruginibacter profundus sp. nov. (type strain DS48-5-3T = KCTC 32478T = JCM 19431T), is proposed. 相似文献
214.
215.
Eun-Jung Kim Hyeoncheol Francis Son Sangwoo Kim Jae-Woo Ahn Kyung-Jin Kim 《Biochemical and biophysical research communications》2014
ReBktB is a β-keto thiolase from Ralstonia eutropha H16 that catalyzes condensation reactions between acetyl-CoA with acyl-CoA molecules that contains different numbers of carbon atoms, such as acetyl-CoA, propionyl-CoA, and butyryl-CoA, to produce valuable bioproducts, such as polyhydroxybutyrate, polyhydroxybutyrate-hydroxyvalerate, and hexanoate. We solved a crystal structure of ReBktB at 2.3 Å, and the overall structure has a similar fold to that of type II biosynthetic thiolases, such as PhbA from Zoogloea ramigera (ZrPhbA). The superposition of this structure with that of ZrPhbA complexed with CoA revealed the residues that comprise the catalytic and substrate binding sites of ReBktB. The catalytic site of ReBktB contains three conserved residues, Cys90, His350, and Cys380, which may function as a covalent nucleophile, a general base, and second nucleophile, respectively. For substrate binding, ReBktB stabilized the ADP moiety of CoA in a distinct way compared to ZrPhbA with His219, Arg221, and Asp228 residues, whereas the stabilization of β-mercaptoethyamine and pantothenic acid moieties of CoA was quite similar between these two enzymes. Kinetic study of ReBktB revealed that Km, Vmax, and Kcat values of 11.58 μM, 1.5 μmol/min, and 102.18 s−1, respectively, and the catalytic and substrate binding sites of ReBktB were further confirmed by site-directed mutagenesis experiments. 相似文献
216.
Yun-Hee Rhee Phil-Sang Chung Sung-Hoon Kim Jin Chul Ahn 《Biochemical and biophysical research communications》2014
Anethole has been known to have chemopreventive activities as a suppressor of the incidence and multiplicity of both invasive and noninvasive carcinomas. The goal of this study was to understand the anti-metastatic effect of anethole through C-X-C chemokine receptor type 4 (CXCR4)/tumor suppressor phosphatase and tensin homologue (PTEN) axis in DU145 prostate cancer cells. Anethole reduced both of the RNA level and the protein level of CXCR4 in a dose-dependent manner without cytotoxicity. Anethole also reduced the expression of CXCR4 and prolonged the expression of PTEN in DU145 prostate cancers. The phosphorylation of AKT and phosphatidylinositol-3kinase (PI3K) were decreased with anethole. The inhibition metastatic effect of anethole was arisen from down-regulating CXCR4 and up-regulating PTEN. Morphologically, anethole significantly inhibited the invasion of DU145 cell and down-regulated the activities of matrix-metalloproteinase (MMPs) in a dose-dependent manner. However, anethole didnot decrease the phosphorylation of PI3K and AKT while PTEN was silenced. Furthermore, the CXCR4 inhibition of anethole was not caused to proteasomal or lysosomal of CXCR4. 相似文献
217.
218.
Sumei Liao Marlise I. Klein Kyle P. Heim Yuwei Fan Jacob P. Bitoun San-Joon Ahn Robert A. Burne Hyun Koo L. Jeannine Brady Zezhang T. Wen 《Journal of bacteriology》2014,196(13):2355-2366
Streptococcus mutans, a major etiological agent of human dental caries, lives primarily on the tooth surface in biofilms. Limited information is available concerning the extracellular DNA (eDNA) as a scaffolding matrix in S. mutans biofilms. This study demonstrates that S. mutans produces eDNA by multiple avenues, including lysis-independent membrane vesicles. Unlike eDNAs from cell lysis that were abundant and mainly concentrated around broken cells or cell debris with floating open ends, eDNAs produced via the lysis-independent pathway appeared scattered but in a structured network under scanning electron microscopy. Compared to eDNA production of planktonic cultures, eDNA production in 5- and 24-h biofilms was increased by >3- and >1.6-fold, respectively. The addition of DNase I to growth medium significantly reduced biofilm formation. In an in vitro adherence assay, added chromosomal DNA alone had a limited effect on S. mutans adherence to saliva-coated hydroxylapatite beads, but in conjunction with glucans synthesized using purified glucosyltransferase B, the adherence was significantly enhanced. Deletion of sortase A, the transpeptidase that covalently couples multiple surface-associated proteins to the cell wall peptidoglycan, significantly reduced eDNA in both planktonic and biofilm cultures. Sortase A deficiency did not have a significant effect on membrane vesicle production; however, the protein profile of the mutant membrane vesicles was significantly altered, including reduction of adhesin P1 and glucan-binding proteins B and C. Relative to the wild type, deficiency of protein secretion and membrane protein insertion machinery components, including Ffh, YidC1, and YidC2, also caused significant reductions in eDNA. 相似文献
219.
Fenofibrate but not fenofibric acid inhibits 11beta-hydroxysteroid dehydrogenase 1 in C2C12 myotubes
Chi Hyun Kim Ravirala Ramu Jin Hee Ahn Myung Ae Bae Young Sik Cho 《Molecular and cellular biochemistry》2010,333(1-2):91-98
Microtubules (MTs) play an important role in cell division, and their functions are regulated by a set of microtubule-associated proteins (MAPs). Tubulin polymerization promoting protein family member 3 (TPPP3), also known as p20, is a new member of the tubulin polymerization promoting protein (TPPP) family. Previous studies have demonstrated that TPPP3 specifically binds to MTs and positively regulates MTs assembly, which leads to significant ultrastructural alterations of the MTs network. However, the physiological function of TPPP3 is still largely unknown. In the present study, we showed that knockdown of endogenous TPPP3 by RNA interference (RNAi) suppressed cell proliferation and induced cell cycle arrest in HeLa cells. Furthermore, we showed that the depletion of TPPP3 caused mitotic abnormalities, such as the formation of multipolar spindles and chromosome segregation errors, which lead to apoptosis in HeLa cells. Our study suggested that TPPP3 played a crucial role in cell mitosis by regulating centrosomes amplification and/or spindles translocation processes. 相似文献
220.
Ji-Hye Yoon Soo-A Kim Seong-Min Kwon Jong-Hwan Park Hee-Sae Park Yong-Chul Kim Jung-Hoon Yoon Sang-Gun Ahn 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010