全文获取类型
收费全文 | 1319篇 |
免费 | 88篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 6篇 |
2022年 | 10篇 |
2021年 | 24篇 |
2020年 | 15篇 |
2019年 | 19篇 |
2018年 | 24篇 |
2017年 | 19篇 |
2016年 | 44篇 |
2015年 | 80篇 |
2014年 | 84篇 |
2013年 | 100篇 |
2012年 | 117篇 |
2011年 | 114篇 |
2010年 | 79篇 |
2009年 | 60篇 |
2008年 | 82篇 |
2007年 | 84篇 |
2006年 | 76篇 |
2005年 | 76篇 |
2004年 | 70篇 |
2003年 | 59篇 |
2002年 | 49篇 |
2001年 | 18篇 |
2000年 | 16篇 |
1999年 | 11篇 |
1998年 | 15篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 8篇 |
1993年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1965年 | 2篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有1408条查询结果,搜索用时 78 毫秒
21.
Yongsung Hwang Samuel Suk Susan Lin Matthew Tierney Bin Du Timothy Seo Aaron Mitchell Alessandra Sacco Shyni Varghese 《PloS one》2013,8(8)
Development of human embryonic stem cell (hESC)-based therapy requires derivation of in vitro expandable cell populations that can readily differentiate to specified cell types and engraft upon transplantation. Here, we report that hESCs can differentiate into skeletal muscle cells without genetic manipulation. This is achieved through the isolation of cells expressing a mesodermal marker, platelet-derived growth factor receptor-α (PDGFRA), following embryoid body (EB) formation. The ESC-derived cells differentiated into myoblasts in vitro as evident by upregulation of various myogenic genes, irrespective of the presence of serum in the medium. This result is further corroborated by the presence of sarcomeric myosin and desmin, markers for terminally differentiated cells. When transplanted in vivo, these pre-myogenically committed cells were viable in tibialis anterior muscles 14 days post-implantation. These hESC-derived cells, which readily undergo myogenic differentiation in culture medium containing serum, could be a viable cell source for skeletal muscle repair and tissue engineering to ameliorate various muscle wasting diseases. 相似文献
22.
Mi Kyung Kwak Daniel T. Johnson Chunfang Zhu Suk Hyung Lee Ding-Wei Ye Richard Luong Zijie Sun 《PloS one》2013,8(1)
The PTEN tumor suppressor gene is frequently inactivated in human prostate cancer. Using Osr1 (odd skipped related 1)-Cre mice, we generated a novel conditional Pten knockout mouse strain, PtenLoxP:Osr1-Cre. Conditional biallelic and monoallelic Pten knockout mice were viable. Deletion of Pten expression was detected in the prostate of PtenLoxP/LoxP:Osr1-Cre mice as early as 2 weeks of age. Intriguingly, PtenLoxP/LoxP:Osr1-Cre mice develop high-grade prostatic intraepithelial neoplasms (PINs) with high penetrance as early as one-month of age, and locally invasive prostatic tumors after 12-months of age. PtenLoxP/+:Osr1-Cre mice show only mild oncogenic changes after 8-weeks of age. Castration of PtenLoxP/LoxP:Osr1-Cre mice shows no significant regression of prostate tumors, although a shift of androgen receptor (AR) staining from the nuclei to cytoplasm is observed in Pten null tumor cells of castrated mice. Enhanced Akt activity is observed in Pten null tumor cells of castrated PtenLoxP/LoxP:Osr1-Cre. This study provides a novel mouse model that can be used to investigate a primary role of Pten in initiating oncogenic transformation in the prostate and to examine other genetic and epigenetic changes that are required for tumor progression in the mouse prostate. 相似文献
23.
Bo-Mi Hwang Hee Suk Chae Young-Ju Jeong Young-Rae Lee Eun-Mi Noh Hyun Zo Youn Sung Hoo Jung Hong-Nu Yu Eun Yong Chung Jong-Suk Kim 《BMB reports》2013,46(11):533-538
The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy-3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-κB activation in TPA-treated MCF-7 cells. However, BVT948 didn’t block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9. [BMB Reports 2013; 46(11): 533-538] 相似文献
24.
25.
Young-Jun Park Sung-Jin Yoon Hyun-Woo Suh Dong Oh Kim Jeong-Ran Park Haiyoung Jung Tae-Don Kim Suk Ran Yoon Jeong-Ki Min Hee-Jun Na Seon-Jin Lee Hee Gu Lee Young Ho Lee Hee-Bong Lee Inpyo Choi 《PLoS pathogens》2013,9(10)
Thioredoxin-interacting protein (TXNIP) has multiple functions, including tumor suppression and involvement in cell proliferation and apoptosis. However, its role in the inflammatory process remains unclear. In this report, we demonstrate that Txnip−/− mice are significantly more susceptible to lipopolysaccharide (LPS)-induced endotoxic shock. In response to LPS, Txnip−/− macrophages produced significantly higher levels of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), and an iNOS inhibitor rescued Txnip−/− mice from endotoxic shock-induced death, demonstrating that NO is a major factor in TXNIP-mediated endotoxic shock. This susceptibility phenotype of Txnip−/− mice occurred despite reduced IL-1β secretion due to increased S-nitrosylation of NLRP3 compared to wild-type controls. Taken together, these data demonstrate that TXNIP is a novel molecule that links NO synthesis and NLRP3 inflammasome activation during endotoxic shock. 相似文献
26.
Min Jeong Ryu Soung Jung Kim Yong Kyung Kim Min Jeong Choi Surendar Tadi Min Hee Lee Seong Eun Lee Hyo Kyun Chung Saet Byel Jung Hyun-Jin Kim Young Suk Jo Koon Soon Kim Sang-Hee Lee Jin Man Kim Gi Ryang Kweon Ki Cheol Park Jung Uee Lee Young Yun Kong Chul-Ho Lee Jongkyeong Chung Minho Shong 《PLoS genetics》2013,9(3)
Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. 相似文献
27.
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
28.
Hong Sung Hyun Singh Sudhir Tripathi Bhumi Nath Mondal Suvendu Lee Sangmin Jung Hyun Suk Cho Chuloh Kaur Shubhpreet Kim Jin-Hong Lee Sungbeom Bai Hyoung-Woo Bae Hyeun-Jong Lee Sang Yeol Lee Seung Sik Chung Byung Yeoup 《Protoplasma》2020,257(3):807-817
Protoplasma - Alkyl hydroperoxide reductase subunit F (AhpF) is a well-known flavoprotein that transfers electrons from pyridine nucleotides to the peroxidase protein AhpC via redox-active... 相似文献
29.
Jung Hwan Yoon Mi La Cho Yoo Jin Choi Ji Yeon Back Mi Kyung Park Suk Woo Lee Byung Joon Choi Hassan Ashktorab Duane T. Smoot Suk Woo Nam Jung Young Lee Won Sang Park 《Journal of cellular biochemistry》2013,114(8):1800-1809
Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. In this study, we examined the effect of GKN1 on the expression of inflammatory mediators, including NF‐κB, COX‐2, and cytokines in GKN1‐transfected AGS cells and shGKN1‐transfected HFE‐145 cells. Lymphocyte migration and cell viability were also analyzed after treatment with GKN1 and inflammatory cytokines in AGS cells by transwell chemotaxis and an MTT assay, respectively. In GKN1‐transfected AGS cells, we observed inactivation and reduced expression of NF‐κB and COX‐2, whereas shGKN1‐transfected HFE‐145 cells showed activation and increased expression of NF‐κB and COX‐2. GKN1 expression induced production of inflammatory cytokines including IL‐8 and ‐17A, but decreased expression of IL‐6 and ‐10. We also found IL‐17A expression in 9 (13.6%) out of 166 gastric cancer tissues and its expression was closely associated with GKN1 expression. GKN1 also acted as a chemoattractant for the migration of Jurkat T cells and peripheral B lymphocytes in the transwell assay. In addition, GKN1 significantly reduced cell viability in both AGS and HFE‐145 cells. These data suggest that the GKN1 gene may inhibit progression of gastric epithelial cells to cancer cells by regulating NF‐κB signaling pathway and cytokine expression. J. Cell. Biochem. 114: 1800–1809, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
30.
Suk Jun Lee Joonbeom Bae Sunhee Kim Seonah Jeong Chang-Yong Choi Sang-Pil Choi Hyun-Sook Kim Woon-Won Jung Jee-Young Imm Sae Hun Kim Taehoon Chun 《Biotechnology letters》2013,35(2):165-173
Treatment of helper T (Th) cells with saponins from soy bean and mung bean prevented their activation by inhibiting cell proliferation and cytokine secretion. However, the saponins did not affect the expression of major histocompatibility complex class II (Ab) and co-stimulatory molecule (CD86) on professional antigen-presenting cells. Instead, the saponins directly inhibited Th cell proliferation by blocking the G1 to S phase cell cycle transition. Moreover, blocking of the cell cycle by the saponins was achieved by decreased expression of cyclin D1 and cyclin E, and constitutive expression of p27KIP1. Saponins also increased stability of p27KIP1 in Th cells after antigenic stimulation. 相似文献