全文获取类型
收费全文 | 5894篇 |
免费 | 428篇 |
国内免费 | 5篇 |
专业分类
6327篇 |
出版年
2024年 | 8篇 |
2023年 | 27篇 |
2022年 | 97篇 |
2021年 | 128篇 |
2020年 | 100篇 |
2019年 | 117篇 |
2018年 | 205篇 |
2017年 | 160篇 |
2016年 | 255篇 |
2015年 | 396篇 |
2014年 | 398篇 |
2013年 | 440篇 |
2012年 | 570篇 |
2011年 | 508篇 |
2010年 | 304篇 |
2009年 | 276篇 |
2008年 | 370篇 |
2007年 | 375篇 |
2006年 | 297篇 |
2005年 | 262篇 |
2004年 | 249篇 |
2003年 | 229篇 |
2002年 | 164篇 |
2001年 | 94篇 |
2000年 | 81篇 |
1999年 | 69篇 |
1998年 | 32篇 |
1997年 | 25篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1971年 | 2篇 |
排序方式: 共有6327条查询结果,搜索用时 15 毫秒
51.
Jung Ok Park Do‐Young Choi Dong‐Sic Choi Hee Joung Kim Jeong Won Kang Jae Hun Jung Jeong Hwa Lee Jayoung Kim Michael R. Freeman Kye Young Lee Yong Song Gho Kwang Pyo Kim 《Proteomics》2013,13(14):2125-2134
Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano‐LC–MS/MS following 1D SDS‐PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung‐enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. 相似文献
52.
Young-Hoon Park Mi Suk Jeong Hyun Ho Park Se Bok Jang 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):292-300
Fas-associated death domain (FADD) protein is an adapter molecule that bridges the interactions between membrane death receptors and initiator caspases. The death receptors contain an intracellular death domain (DD) which is essential to the transduction of the apoptotic signal. The kinase receptor-interacting protein 1 (RIP1) is crucial to programmed necrosis. The cell type interplay between FADD and RIP1, which mediates both necrosis and NF-κB activation, has been evaluated in other studies, but the mechanism of the interaction of the FADD and RIP1 proteins remain poorly understood. Here, we provided evidence indicating that the DD of human FADD binds to the DD of RIP1 in vitro. We developed a molecular docking model using homology modeling based on the structures of FADD and RIP1. In addition, we found that two structure-based mutants (G109A and R114A) of the FADD DD were able to bind to the RIP1 DD, and two mutations (Q169A and N171A) of FADD DD and four mutations (G595, K596, E620, and D622) of RIP1 DD disrupted the FADD–RIP1 interaction. Six mutations (Q169A, N171A, G595, K596, E620, and D622) lowered the stability of the FADD–RIP1 complex and induced aggregation that structurally destabilized the complex, thus disrupting the interaction. 相似文献
53.
Kwangsoo Kim Jae Ho Jeong Daejin Lim Yeongjin Hong Misun Yun Jung-Joon Min Sahng-June Kwak Hyon E. Choy 《PloS one》2013,8(3)
During the last decade, an increasing number of papers have described the use of various genera of bacteria, including E. coli and S. typhimurium, in the treatment of cancer. This is primarily due to the facts that not only are these bacteria capable of accumulating in the tumor mass, but they can also be engineered to deliver specific therapeutic proteins directly to the tumor site. However, a major obstacle exists in that bacteria because the plasmid carrying the therapeutic gene is not needed for bacterial survival, these plasmids are often lost from the bacteria. Here, we report the development of a balanced-lethal host-vector system based on deletion of the glmS gene in E. coli and S. typhimurium. This system takes advantage of the phenotype of the GlmS− mutant, which undergoes lysis in animal systems that lack the nutrients required for proliferation of the mutant bacteria, D-glucosamine (GlcN) or N-acetyl-D-glucosamine (GlcNAc), components necessary for peptidoglycan synthesis. We demonstrate that plasmids carrying a glmS gene (GlmS+p) complemented the phenotype of the GlmS− mutant, and that GlmS+p was maintained faithfully both in vitro and in an animal system in the absence of selection pressure. This was further verified by bioluminescent signals from GlmS
+pLux carried in bacteria that accumulated in grafted tumor tissue in a mouse model. The signal was up to several hundred-fold stronger than that from the control plasmid, pLux, due to faithful maintenance of the plasmid. We believe this system will allow to package a therapeutic gene onto an expression plasmid for bacterial delivery to the tumor site without subsequent loss of plasmid expression as well as to quantify bioluminescent bacteria using in vivo imaging by providing a direct correlation between photon flux and bacterial number. 相似文献
54.
Mina Lee Song E. Kim Won Sup Kim Jungyeun Lee Hye Kyung Yoo Kee-Duk Park Kyoung-Gyu Choi Seon-Yong Jeong Byung Gon Kim Hyang Woon Lee 《PloS one》2013,8(2)
Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities. 相似文献
55.
56.
Jinhua Dong Yuya Oka Hee-Jin Jeong Yuki Ohmuro-Matsuyama Hiroshi Ueda 《Biotechnology and bioengineering》2020,117(5):1259-1269
Ultra Quenchbody (UQ-body) is a biosensor that utilizes the quenching behavior of the fluorescent dye linked to the antibody V region. When the corresponding antigen is bound to the UQ-body, the fluorescence is restored and allows the detection of target molecules easily and sensitively. In this paper, we constructed UQ-bodies to sensitively detect the human epidermal growth factor receptor 2 (HER2) cancer marker in solution or on cancer cells, which was further used to kill the cancer cells. A synthetic Fab fragment of anti-HER2 antibody Fab37 with many Trp residues at hypervariable region was prepared and labeled with fluorescent dyes to obtain the UQ-bodies. The UQ-body could detect HER2 in solution at concentrations as low as 20 pM with an EC50 of 0.3 nM with a fourfold response. Fluorescence imaging of HER2-positive cells was successfully performed without any washing steps. To deliver small interfering RNA (siRNA) to cancer cells, a modified UQ-body with C-terminal 9R sequence was also prepared. HER2-positive cancer cells were effectively killed by polo-like kinase 1 siRNA intracellularly delivered by the UQ-body-9R. The novel approach employing siRNA-empowered UQ-body could detect and image the HER2 antigen easily and sensitively, and effectively kill the HER2-positive cancer cells. 相似文献
57.
Jeong Won Kang Young Gyu Choi Jun Ha Lee Oh Kuen Kwon Ho Jung Hwang 《Molecular simulation》2013,39(9):829-835
Pure carbon nanotube (CNT) oscillators are compared to the corresponding CNT oscillators encapsulating copper nanowires (Cu@CNTs) by molecular dynamics simulations. The classical oscillation theory provides a fairly good estimate of the mass dependence of the operating frequency when the CNT surface is not deformed by the Cu nanowire. The structural deformations of the CNT induced by the encapsulated copper nanowire have a greater effect on the oscillation frequency than the mass of the copper nanowire. The excess forces of the Cu@CNT oscillator are slightly higher than those of the CNT oscillator and the excess van der Waals forces induced by the inter-wall interactions are 17 times higher than the excess forces induced by the Cu nanowire–CNT interactions. 相似文献
58.
59.
Man Sub Kim Yesol Bak Yun Sun Park Dong Hun Lee Jung Hee Kim Jeong Woo Kang Hyuk-Hwan Song Sei-Ryang Oh Do Young Yoon 《Cell biology and toxicology》2013,29(4):259-272
Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is well known as a benzodiazepine receptor ligand with anxiolytic effects. Many recent studies have demonstrated that wogonin modulates angiogenesis, proliferation, invasion, and tumor progress in various cancer tissues. We further explored the mechanism of action of wogonin on cervical cancer cells that contain or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+) cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We demonstrated that wogonin induced apoptosis by suppressing the expressions of the E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells. The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the suppression of E6 and E7 expressions. However, p53 was not altered in HPV-negative cervical cancer C33A cells. Moreover, wogonin modulated the mitochondrial membrane potential and the expression of pro- and anti-apoptotic factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3, caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target E6 and E7, additional restoration of p53 and pRb was not induced, but processing of caspases and PARP was increased compared with wogonin treatment alone. Together, our findings demonstrated that wogonin effectively promotes apoptosis by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in human cervical cancer cells. 相似文献