全文获取类型
收费全文 | 7391篇 |
免费 | 606篇 |
国内免费 | 4篇 |
出版年
2024年 | 7篇 |
2023年 | 25篇 |
2022年 | 76篇 |
2021年 | 169篇 |
2020年 | 124篇 |
2019年 | 172篇 |
2018年 | 244篇 |
2017年 | 196篇 |
2016年 | 300篇 |
2015年 | 423篇 |
2014年 | 494篇 |
2013年 | 531篇 |
2012年 | 708篇 |
2011年 | 613篇 |
2010年 | 392篇 |
2009年 | 350篇 |
2008年 | 503篇 |
2007年 | 483篇 |
2006年 | 401篇 |
2005年 | 356篇 |
2004年 | 397篇 |
2003年 | 295篇 |
2002年 | 243篇 |
2001年 | 90篇 |
2000年 | 84篇 |
1999年 | 67篇 |
1998年 | 62篇 |
1997年 | 25篇 |
1996年 | 22篇 |
1995年 | 19篇 |
1994年 | 17篇 |
1993年 | 8篇 |
1992年 | 18篇 |
1991年 | 18篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 3篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1968年 | 1篇 |
1965年 | 2篇 |
1963年 | 1篇 |
1960年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有8001条查询结果,搜索用时 15 毫秒
101.
Dong Hoon Shin Gyeong Im Yu Jae Seok Hwang Eun Soo Kim Jong Won Yun 《Proteomics》2013,13(15):2361-2374
In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine‐rich α‐2‐glycoprotein, hemoglobin subunit β, Ig α‐2 chain C region, and complement factor B as well as downregulated afamin, zinc‐α‐2‐glycoprotein, vitronectin, and α‐1‐antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin‐8, interferon gamma‐induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma. 相似文献
102.
Sajeesh Kappachery Jae Woong Yu Gangadhar Baniekal-Hiremath Se Won Park 《Comptes rendus biologies》2013,336(11-12):530-545
Identification of major stress tolerance genes of a crop plant is important for the rapid development of its stress-tolerant cultivar. Here, we used a yeast functional screen method to identify potential drought-tolerance genes from a potato plant. A cDNA expression library was constructed from hyperosmotic stressed potato plants. The yeast transformants expressing different cDNAs were selected for their ability to survive in hyperosmotic stress conditions. The relative tolerances of the selected yeast transformants to multiple abiotic stresses were also studied. Specific potato cDNAs expressed in the tolerant yeast transformants were identified. Sixty-nine genes were found capable of enhancing hyperosmotic stress tolerance of yeast. Based on the relative tolerance data generated, 12 genes were selected, which could be most effective in imparting higher drought tolerance to potato with better survival in salt and high-temperature stresses. Orthologues of few genes identified here are previously known to increase osmotic stress tolerance of yeast and plants; however, specific studies are needed to confirm their role in the osmotic stress tolerance of potato. 相似文献
103.
104.
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
105.
Yuwon Park Nam‐Soon Choi Sangjin Park Seung Hee Woo Soojin Sim Bo Yun Jang Seung M. Oh Soojin Park Jaephil Cho Kyu Tae Lee 《Liver Transplantation》2013,3(2):206-212
Remarkable improvements in the electrochemical performance of Si materials for Li‐ion batteries have been recently achieved, but the inherent volume change of Si still induces electrode expansion and external cell deformation. Here, the void structure in Si‐encapsulating hollow carbons is optimized in order to minimize the volume expansion of Si‐based anodes and improve electrochemical performance. When compared to chemical etching, the hollow structure is achieved via electroless etching is more advanced due to the improved electrical contact between carbon and Si. Despite the very thick electrodes (30 ~ 40 μm), this results in better cycle and rate performances including little capacity fading over 50 cycles and 1100 mA h g?1 at 2C rate. Also, an in situ dilatometer technique is used to perform a comprehensive study of electrode thickness change, and Si‐encapsulating hollow carbon mitigates the volume change of electrodes by adoption of void space, resulting in a small volume increase of 18% after full lithiation corresponding with a reversible capacity of about 2000 mA h g?1. 相似文献
106.
In-Gyun Lee Sun-Bok Jang Ji-Hun Kim Ki-Young Lee Kyu-Yeon Lee Hae-Kap Cheong Bong-Jin Lee 《Biomolecular NMR assignments》2013,7(2):159-162
Cell adhesion molecules play a crucial role in fundamental biological processes via regulating cell–cell interactions. Nerve injury induced protein1 (Ninjurin1) is a novel adhesion protein that has no significant homology with other known cell adhesion molecules. Here we present the assignment of an 81 aa construct for human Ninjurin1 Extracellular N-Terminal (ENT) domain, which comprises the critical adhesion domain. 相似文献
107.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
108.
Jong-Seok Kim Woo Sik Kim Keehoon Lee Choul-Jae Won Jin Man Kim Seok-Yong Eum Won-Jung Koh Sung Jae Shin 《PloS one》2013,8(3)
Two closely related bacterial species, Segniliparus rotundus and Segniliparus rugosus, have emerged as important human pathogens, but little is known about the immune responses they elicit or their comparative pathophysiologies. To determine the virulence and immune responses of the two species, we compared their abilities to grow in phagocytic and non-phagocytic cells. Both species maintained non-replicating states within A549 epithelial cells. S. rugosus persisted longer and multiplied more rapidly inside murine bone marrow-derived macrophages (BMDMs), induced more pro-inflammatory cytokines, and induced higher levels of macrophage necrosis. Activation of BMDMs by both species was mediated by toll-like receptor 2 (TLR2), followed by mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) signaling pathways, indicating a critical role for TLR2 in Segniliparus-induced macrophage activation. S. rugosus triggered faster and stronger activation of MAPK signaling and IκB degradation, indicating that S. rugosus induces more pro-inflammatory cytokines than S. rotundus. Multifocal granulomatous inflammations in the liver and lung were observed in mice infected with S. rugosus, but S. rotundus was rapidly cleared from all organs tested within 15 days post-infection. Furthermore, S. rugosus induced faster infiltration of innate immune cells such as neutrophils and macrophages to the lung than S. rotundus. Our results suggest that S. rugosus is more virulent and induces a stronger immune response than S. rotundus. 相似文献
109.
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
110.
Jae Young So Amanda K. Smolarek David M. Salerno Hubert Maehr Milan Uskokovic Fang Liu Nanjoo Suh 《PloS one》2013,8(1)