全文获取类型
收费全文 | 2841篇 |
免费 | 178篇 |
国内免费 | 10篇 |
出版年
2024年 | 5篇 |
2023年 | 29篇 |
2022年 | 81篇 |
2021年 | 124篇 |
2020年 | 104篇 |
2019年 | 150篇 |
2018年 | 123篇 |
2017年 | 91篇 |
2016年 | 118篇 |
2015年 | 148篇 |
2014年 | 161篇 |
2013年 | 220篇 |
2012年 | 213篇 |
2011年 | 218篇 |
2010年 | 128篇 |
2009年 | 96篇 |
2008年 | 104篇 |
2007年 | 112篇 |
2006年 | 115篇 |
2005年 | 84篇 |
2004年 | 77篇 |
2003年 | 53篇 |
2002年 | 52篇 |
2001年 | 15篇 |
2000年 | 25篇 |
1999年 | 26篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 12篇 |
1993年 | 8篇 |
1992年 | 21篇 |
1991年 | 17篇 |
1990年 | 20篇 |
1989年 | 21篇 |
1988年 | 35篇 |
1987年 | 23篇 |
1986年 | 9篇 |
1985年 | 15篇 |
1984年 | 25篇 |
1983年 | 15篇 |
1982年 | 12篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1973年 | 9篇 |
1969年 | 9篇 |
1967年 | 4篇 |
排序方式: 共有3029条查询结果,搜索用时 171 毫秒
101.
Yaghoub Yazdani Neda Keyhanvar Hamid Reza Kalhor Abbas Rezaei 《Biotechnology letters》2013,35(8):1191-1197
Hepcidin is a peptide hormone that plays an important role in iron metabolism. We have produced a recombinant mouse hepcidin-1 by using baculovirus expression system. Its expression yield was 25 μg/ml when cell culture media were supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1 and synthetic human hepcidin-25 had similar effects on reducing ferroportin expression in J774A cell line and in peritoneal macrophages. However, synthetic human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in reducing iron concentration in blood circulation (p < 0.01). 相似文献
102.
Maryam Pakfetrat Jamshid Roozbeh Shahroodi Ali Asgar Zolgadr Hasan Amin Larie Mohamad Hosein Nikoo Leila Malekmakan 《Biological trace element research》2013,153(1-3):11-15
Increased homocysteine (hCys) level is an independent risk factor for cardiovascular complications in end-stage renal disease (ESRD) patients. The aim of this study was to evaluate effect of zinc (Zn) supplement on serum hCys level in ESRD patients. One hundred ESRD patients with Zn deficiency were enrolled in this double-blind randomized clinical trial. They were randomly subdivided into two groups and supplemented with Zn (Zn group) or placebo (control group) for 6 weeks. Fasting plasma hCys and Zn levels were measured before and at 43rd days after the start of the study. Serum Zn levels increased significantly (p?<?0.0001), in Zn-treated group in comparison to placebo-treated group. In the Zn-treated group, serum hCys levels reduced significantly (p?<?0.0001), compared to placebo group (p?>?0.05). There was a significant (p?<?0.0001) reduction of mean percentage of hCys in Zn-treated group compared to the placebo group. Our study showed that Zn supplementation decreases serum hCys levels in ESRD patients with Zn deficiency. 相似文献
103.
104.
Vishal M. Gohil Lin Zhu Charli D. Baker Valentin Cracan Abbas Yaseen Mohit Jain Clary B. Clish Paul S. Brookes Marica Bakovic Vamsi K. Mootha 《The Journal of biological chemistry》2013,288(49):35387-35395
We recently identified meclizine, an over-the-counter drug, as an inhibitor of mitochondrial respiration. Curiously, meclizine blunted respiration in intact cells but not in isolated mitochondria, suggesting an unorthodox mechanism. Using a metabolic profiling approach, we now show that treatment with meclizine leads to a sharp elevation of cellular phosphoethanolamine, an intermediate in the ethanolamine branch of the Kennedy pathway of phosphatidylethanolamine biosynthesis. Metabolic labeling and in vitro enzyme assays confirmed direct inhibition of the cytosolic enzyme CTP:phosphoethanolamine cytidylyltransferase (PCYT2). Inhibition of PCYT2 by meclizine led to rapid accumulation of its substrate, phosphoethanolamine, which is itself an inhibitor of mitochondrial respiration. Our work identifies the first pharmacologic inhibitor of the Kennedy pathway, demonstrates that its biosynthetic intermediate is an endogenous inhibitor of respiration, and provides key mechanistic insights that may facilitate repurposing meclizine for disorders of energy metabolism. 相似文献
105.
Amir Assadieskandar Amirali Amirhamzeh Marjan Salehi Keriman Ozadali Seyed Nasser Ostad Abbas Shafiee Mohsen Amini 《Bioorganic & medicinal chemistry》2013,21(8):2355-2362
A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively. 相似文献
106.
Mehdi Khoshneviszadeh Mohammad H. Ghahremani Alireza Foroumadi Ramin Miri Omidreza Firuzi Armin Madadkar-Sobhani Najmeh Edraki Maliheh Parsa Abbas Shafiee 《Bioorganic & medicinal chemistry》2013,21(21):6708-6717
A series of 16 novel 1,2,4-triazine derivatives bearing hydrazone moiety (7a–7p) have been designed, synthesized and evaluated for their activity to inhibit IL-1β and TNF-α production. All compounds are reported for the first time. The chemical structures of all compounds were confirmed by spectroscopic methods and elemental analyzes. Most of the synthesized compounds were proved to have potent anti-cytokine activity and low toxicity on PBMC and MCF-7 cell lines. Compounds 7f, 7k, 7l and 7j presented simultaneously good levels of inhibition of both cytokines. Moreover, compound 7l exhibited good anti-inflammatory effect in carrageenan-induced rat paw edema. The results of Western blotting demonstrated that the anti-cytokine potential of compound 7l is mainly mediated through the inhibition of p38 MAPK signaling pathway. Molecular docking was performed to position compound 7l into p38α binding site in order to explore the potential target. The information of this work might be helpful for the design and synthesis of novel scaffold toward the development of new therapeutic agent to fight against inflammatory diseases. 相似文献
107.
108.
Jin Wang Ping Liu Mary F.H. She Saeid Nahavandi Abbas Kouzani 《Biomedical signal processing and control》2013,8(6):634-644
Automatic analysis of biomedical time series such as electroencephalogram (EEG) and electrocardiographic (ECG) signals has attracted great interest in the community of biomedical engineering due to its important applications in medicine. In this work, a simple yet effective bag-of-words representation that is originally developed for text document analysis is extended for biomedical time series representation. In particular, similar to the bag-of-words model used in text document domain, the proposed method treats a time series as a text document and extracts local segments from the time series as words. The biomedical time series is then represented as a histogram of codewords, each entry of which is the count of a codeword appeared in the time series. Although the temporal order of the local segments is ignored, the bag-of-words representation is able to capture high-level structural information because both local and global structural information are well utilized. The performance of the bag-of-words model is validated on three datasets extracted from real EEG and ECG signals. The experimental results demonstrate that the proposed method is not only insensitive to parameters of the bag-of-words model such as local segment length and codebook size, but also robust to noise. 相似文献
109.
Sanjeev Shukla Haripaul Sharma Ata Abbas Gregory T. MacLennan Pingfu Fu David Danielpour Sanjay Gupta 《PloS one》2013,8(1)
Disease aggressiveness remains a critical factor to the progression of prostate cancer. Transformation of epithelial cells to mesenchymal lineage, associated with the loss of E-cadherin, offers significant invasive potential and migration capability. Recently, Special AT-rich binding protein (SATB1) has been linked to tumor progression. SATB1 is a cell-type restricted nuclear protein, which functions as a tissue-specific organizer of DNA sequences during cellular differentiation. Our results demonstrate that SATB1 plays significant role in prostate tumor invasion and migration and its nuclear localization correlates with disease aggressiveness. Clinical specimen analysis showed that SATB1 was predominantly expressed in the nucleus of high-grade tumors compared to low-grade tumor and benign tissue. A progressive increase in the nuclear levels of SATB1 was observed in cancer tissues compared to benign specimens. Similarly, SATB1 protein levels were higher in a number of prostate cancer cells viz. HPV-CA-10, DU145, DUPro, PC-3, PC-3M, LNCaP and C4-2B, compared to non-tumorigenic PZ-HPV-7 cells. Nuclear expression of SATB1 was higher in biologically aggressive subclones of prostate cancer cells with their respective parental cell lines. Furthermore, ectopic SATB1 transfection conferred increased cell motility and invasiveness in immortalized human prostate epithelial PZ-HPV-7 cells which correlated with the loss of E-cadherin expression. Consequently, knockdown of SATB1 in highly aggressive human prostate cancer PC-3M cells inhibited invasiveness and tumor growth in vivo along with increase in E-cadherin protein expression. Our findings demonstrate that SATB1 has ability to promote prostate cancer aggressiveness through epithelial-mesenchymal transition. 相似文献
110.
Plasmonics - In this paper, we propose an ultra-compact high-speed electro-optical modulator with extremely low energy consumption based on silicon-polymer-metal hybrid plasmonic waveguide. Spatial... 相似文献