全文获取类型
收费全文 | 330篇 |
免费 | 15篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 6篇 |
2017年 | 12篇 |
2016年 | 12篇 |
2015年 | 21篇 |
2014年 | 18篇 |
2013年 | 25篇 |
2012年 | 32篇 |
2011年 | 24篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 12篇 |
2006年 | 17篇 |
2005年 | 4篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 7篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 6篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有346条查询结果,搜索用时 15 毫秒
91.
Crider JY Xu SX Sharif NA 《Prostaglandins, leukotrienes, and essential fatty acids》2001,65(5-6):253-258
The objective of these studies was to characterize the effects of a broad range of prostanoid agonists upon the stimulation of cAMP production in National Cancer Bank (NCB-20; mouse neuroblastoma/hamster brain hybridoma) cells. The pharmacology of these functional responses in NCB-20 cells was compared with that of the classic endogenous IP receptor present on human platelets using [3H]-iloprost binding techniques. In both assay systems, agonists from the IP prostanoid class exhibited the highest affinities and functional potencies. Specific prostanoids exhibited the following rank order of potency (EC50 +/- SEM) in stimulating cAMP production in the NCB-20 cells: carbaprostacyclin (4.3 +/- 0.9 nM) = PGI2 (6.6 +/-1.5 nM) > iloprost (75+/-13 nM) > 11-deoxy PGE, (378+/-138 nM) > misoprostol (1,243+/-48) > PGE2 (3020+/-700 nM) > ZK-118182 (7265+/-455 nM). Iloprost wasthe most potent compound in the human platelet binding assay while prostanoidsfromthe DPand EP receptor classes showed modest affinity. These studies provide functional and binding information for a broad range of both natural and synthetic prostanoid receptor ligands at the endogenous IP receptor in two different cell types. 相似文献
92.
Chemical and Surgical Lesions of Rat Olfactory Bulb: Changes in Thyrotropin-Releasing Hormone and Other Systems 总被引:1,自引:0,他引:1
N. A. Sharif 《Journal of neurochemistry》1988,50(2):388-394
Stereotaxic injection of kainic acid (15 micrograms) into rat olfactory bulbs was accompanied by a 53% (n = 4; p less than 0.02) depletion of endogenous thyrotropin-releasing hormone (TRH) as compared to sham-operated controls 2 weeks postlesion. TRH levels remained unaltered in three other caudal regions. Bulbar kainate lesions produced a 58% (n = 5; p less than 0.001) decrease in TRH receptor binding capacity without affecting the receptor affinity. Kainate lesions also reduced bulbar muscarinic and benzodiazepine receptors by 60% and 48%, respectively. Again, no changes in TRH receptors were apparent in six other brain areas after bulbar kainate treatment. Injection of the dopaminergic neurotoxin, 6-hydroxydopamine (8 micrograms), into rat bulbs decreased TRH receptors by 35% (n = 4; p less than 0.05) 1 week postlesion. One month after surgical bulbectomy, TRH and TRH receptor levels in a number of brain areas were unaltered compared to those of control animals. These studies suggest that TRH in the olfactory bulb originates intrinsically and may be produced predominantly for local use. Secondly, TRH receptors in the bulb appear to be postsynaptically localized on intrinsic neurons, although a small proportion are also associated with presynaptic elements of dopaminergic noradrenergic neurons. Bulbar TRH receptors exhibited nanomolar affinity and a pharmacological selectivity akin to that of the pituitary gland and other brain regions. 相似文献
93.
Summary The effect of various doses of copper and zinc on their uptake and on the yield of rice were studied. Copper applications
increased copper contents in the plants without effecting the zinc contents. However, zinc applications though increased zinc
contents but markedly decreased the copper contents in the plants. This antagonistic effect of zinc on copper suggests that
zinc applications can reduce rice yield if available copper is marginal in the soils. re]19720628 相似文献
94.
Naoya Miura Sharif M. Shaheen Hidetaka Akita Takashi Nakamura Hideyoshi Harashima 《Nucleic acids research》2015,43(3):1317-1331
Technologies that delivery antigen-encoded plasmid DNA (pDNA) to antigen presenting cell and their immune-activation are required for the success of DNA vaccines. Here we report on an artificial nanoparticle that can achieve these; a multifunctional envelope-type nanodevice modified with KALA, a peptide that forms α-helical structure at physiological pH (KALA-MEND). KALA modification and the removal of the CpG-motifs from the pDNA synergistically boosted transfection efficacy. In parallel, transfection with the KALA-MEND enhances the production of multiple cytokines and chemokines and co-stimulatory molecules via the Toll-like receptor 9-independent manner. Endosome-fusogenic lipid envelops and a long length of pDNA are essential for this immune stimulation. Furthermore, cytoplasmic dsDNA sensors that are related to the STING/TBK1 pathway and inflammasome are involved in IFN-β and IL-1β production, respectively. Consequently, the robust induction of antigen-specific cytotoxic T-lymphoma activity and the resulting prophylactic and therapeutic anti-tumor effect was observed in mice that had been immunized with bone marrow-derived dendritic cells ex vivo transfected with antigen-encoding pDNA. Collectively, the KALA-MEND possesses dual functions; gene transfection system and immune-stimulative adjuvant, those are both necessary for the successful DNA vaccine. 相似文献
95.
Gouki Okazawa Christina E. Hatch Allan Mancoo Christian K. Machens Roozbeh Kiani 《Cell》2021,184(14):3748-3761.e18
- Download : Download high-res image (184KB)
- Download : Download full-size image
96.
Masoud Yousefi Mohsen Ahmadi Elham Nourani Roozbeh Behrooz Mehdi Rajabizadeh Philippe Geniez Mohammad Kaboli 《PloS one》2015,10(9)
We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC) that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago) and under two scenarios in the future (to 2070). These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region. 相似文献
97.
Xin Wu Hirofumi Yamamoto Hiroyuki Nakanishi Yuki Yamamoto Akira Inoue Mitsuyoshi Tei Hajime Hirose Mamoru Uemura Junichi Nishimura Taishi Hata Ichiro Takemasa Tsunekazu Mizushima Sharif Hossain Toshihiro Akaike Nariaki Matsuura Yuichiro Doki Masaki Mori 《PloS one》2015,10(3)
RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors. 相似文献
98.
99.
Human tissue kallikreins (KLKs) are members of a multigene family of serine proteases aberrantly expressed in many cancer types. In ovarian cancer, 12 KLKs are upregulated, and of those KLK5, 6 and 10 have been the focus of investigations into new diagnostic and prognostic biomarkers. However, little is known about the contributions of KLK5, 6 and 10 to ovarian cancer pathophysiology.In this study, a panel of 13 human ovarian cancer cell lines was screened by ELISA for secretion of KLK5, 6, 8, 10, 13, and 14. The ES-2 cell line, devoid of these kallikreins, was transfected with expression vectors of KLK5, 6 and 10 individually or in pairs. Co-expression of KLK5, 6 and 10 was correlated with lessened aggressivity of ovarian cancer cell lines as defined by reduced colony formation in soft agar and tumorigenicity in nude mice. ES-2 clones overexpressing KLK5, 10/5, 10/6, 5/6 made significantly fewer colonies in soft agar. When compared to control mice, survival of mice injected with ES-2 clones overexpressing KLK10, 10/5, 10/6, 5/6 was significantly longer, while KLK6 was shorter. All groups displaying a survival advantage also differed quantitatively and qualitatively in their presentation of ascites, with both a reduced incidence of ascites and an absence of cellular aggregates within those ascites. The survival advantage conferred by KLK10 overexpression could be recapitulated with the exogenous administration of a recombinant KLK10. In conclusion, these findings indicate that KLK5, 6 and 10 may modulate the progression of ovarian cancer, and interact together to alter tumour pathophysiology. Furthermore, results support the putative role of KLK10 as a tumour suppressor and suggest it may hold therapeutic potential in ovarian cancer. 相似文献
100.
Wanyenze RK Kamya MR Fatch R Mayanja-Kizza H Baveewo S Sawires S Bangsberg DR Coates T Hahn JA 《PloS one》2011,6(7):e21794