全文获取类型
收费全文 | 1039篇 |
免费 | 58篇 |
专业分类
1097篇 |
出版年
2023年 | 3篇 |
2022年 | 19篇 |
2021年 | 25篇 |
2020年 | 7篇 |
2019年 | 12篇 |
2018年 | 21篇 |
2017年 | 25篇 |
2016年 | 19篇 |
2015年 | 40篇 |
2014年 | 38篇 |
2013年 | 61篇 |
2012年 | 59篇 |
2011年 | 57篇 |
2010年 | 45篇 |
2009年 | 36篇 |
2008年 | 55篇 |
2007年 | 53篇 |
2006年 | 53篇 |
2005年 | 42篇 |
2004年 | 43篇 |
2003年 | 56篇 |
2002年 | 41篇 |
2001年 | 28篇 |
2000年 | 28篇 |
1999年 | 42篇 |
1998年 | 3篇 |
1997年 | 10篇 |
1996年 | 10篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 23篇 |
1991年 | 13篇 |
1990年 | 23篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 2篇 |
排序方式: 共有1097条查询结果,搜索用时 15 毫秒
101.
Structure-activity relationship and biological property of cortistatins, anti-angiogenic spongean steroidal alkaloids 总被引:1,自引:0,他引:1
Aoki S Watanabe Y Tanabe D Arai M Suna H Miyamoto K Tsujibo H Tsujikawa K Yamamoto H Kobayashi M 《Bioorganic & medicinal chemistry》2007,15(21):6758-6762
Previously, bioassay-guided separation led us to isolate eleven novel steroidal alkaloids named cortistatins from the marine sponge Corticium simplex. These cortistatins were classified into three types based on the chemical structure of the side chain part, that is, isoquinoline, N-methyl piperidine or 3-methylpyridine units. From the structure-activity relationship study, the isoquinoline unit in the side chain was found to be crucial for the anti-angiogenic activity of cortistatins. Cortistatin A (1) showed cytostatic growth-inhibitory activity against human umbilical vein endothelial cells (HUVECs). Cortistatin A (1) also inhibited VEGF-induced migration of HUVECs and bFGF-induced tubular formation. Although cortistatin A (1) showed no effect on VEGF-induced phosphorylation of ERK1/2 and p38, which are one of the signaling pathways for migration and tubular formation, the phosphorylation of the unidentified 110kDa protein in HUVECs was inhibited by the treatment with cortistatin A. 相似文献
102.
Honda T Shirasu N Isozaki K Kawano M Shigehiro D Chuman Y Fujita T Nose T Shimohigashi Y 《Bioorganic & medicinal chemistry》2007,15(11):3883-3888
Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe(3) and Phe(4) in binding to the mu receptor, we synthesized a series of analogs in which Phe(3) and Phe(4) were replaced by various amino acids. It was found that the aromaticity of the Phe-beta-phenyl groups of Phe(3) and Phe(4) is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe(3) and Phe(4) of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp(3)]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses. 相似文献
103.
Maruyama K Takeyama H Mori T Ohshima K Ogura S Mochizuki T Matsunaga T 《Biosensors & bioelectronics》2007,22(9-10):2282-2288
A fully automated system using nano-scale engineered biomagnetite was developed to detect mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC). Bacterial magnetic particles (BacMPs) were isolated from the magnetic bacterium Magnetospirillum magneticum AMB-1 and conjugated to streptavidin. Biotin-labeled target PCR products were then captured with the BacMPs, hybridized with the detection probe and detected by fluorescence signaling. The process was performed using a newly designed automated processor equipped with an XYZ mobile arm containing a 96-way automated pipetter, reagent dispenser and fluorescence detector. Two types of somatic mutations (in-frame deletions and point substitutions) in the EGFR gene were successfully identified within 3.5h using this system, suggesting that this system could be used in clinical tests of EGFR gene mutations in lung cancer, and potentially other cancer, patients. Additionally, a very low mutation rate could be detected in these samples. 相似文献
104.
105.
Toyoda T Mochizuki Y Player K Heida N Kobayashi N Sakaki Y 《Bioinformatics (Oxford, England)》2007,23(4):524-526
OmicBrowse is a browser to explore multiple datasets coordinated in the multidimensional omic space integrating omics knowledge ranging from genomes to phenomes and connecting evolutional correspondences among multiple species. OmicBrowse integrates multiple data servers into a single omic space through secure peer-to-peer server communications, so that a user can easily obtain an integrated view of distributed data servers, e.g. an integrated view of numerous whole-genome tiling-array data retrieved from a user's in-house private-data server, along with various genomic annotations from public internet servers. OmicBrowse is especially appropriate for positional-cloning purposes. It displays both genetic maps and genomic annotations within wide chromosomal intervals and assists a user to select candidate genes by filtering their annotations or associated documents against user-specified keywords or ontology terms. We also show that an omic-space chart effectively represents schemes for integrating multiple datasets of multiple species. Availability: OmicBrowse is developed by the Genome-Phenome Superbrain Project and is released as free open-source software under the GNU General Public License at http://omicspace.riken.jp. 相似文献
106.
In an investigation of the sporicidal activity of the KMT reagent, a vapor phase study was performed using five kinds of carriers contaminated with Geobacillus stearothermophilus spores. When 25 ml of the KMT reagent was vaporized in a chamber (capacity; approximately 95 liters), the 2-step heating method (vaporization by a combination of low temperature and high temperature) showed the most effective sporicidal activity in comparison with the 1-step heating method (rapid vaporization). The 2-step heating method appeared to be related to the sporicidal activity of vaporized KMT reagent, i.e., ethanol and iodine, which vaporized mainly when heated at a low temperature such as 55 C, and acidic water, which vaporized mainly when heated at a high temperature such as 300 C. We proposed that the KMT reagent can be used as a new disinfectant not only in the liquid phase but also in the vapor phase in the same way as peracetic acid and hydrogen peroxide. 相似文献
107.
Isolation of antioxidative phenolic glucosides from lemon juice and their suppressive effect on the expression of blood adhesion molecules 总被引:2,自引:0,他引:2
Miyake Y Mochizuki M Okada M Hiramitsu M Morimitsu Y Osawa T 《Bioscience, biotechnology, and biochemistry》2007,71(8):1911-1919
Phenolic glucosides having radical scavenging activity were examined from the fraction eluted with 20% methanol on Amberlite XAD-2 resin applied to lemon (Citrus limon) juice by using reversed phase chromatography. Four phenolic glucosides were identified as 1-feruloyl-beta-D-glucopyranoside, 1-sinapoyl-beta-D-glucopyranoside, 6,8-di-C-glucosylapigenin and 6,8-di-C-glucosyldiosmetin by (1)H-NMR, (13)C-NMR, and MS analyses. They exhibited radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide, although the activity was low in comparison with eriocitrin, a potent antioxidant in lemon fruit, and the eriodictyol of its aglycone. The phenolic compounds in lemon juice were examined for their suppressive effect on the expression of blood adhesion molecules by measuring the expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) induced by necrosis factor-alpha (TNF-alpha). 6,8-Di-C-glucosylapigenin, apigenin, and diosmentin of the flavones were found to significantly suppress the expression of ICAM-1 at 10 muM (P<0.05). The phenolic glucosides isolated in this study were contained in comparative abundance in daidai (Citrus aurantium) and niihime (Citrus unshiu x Citrus tachibana) among the sour citrus juices. 相似文献
108.
Jejunal GLUT5 is elevated with triiodothyronine (T(3)) during weaning of rats. A perfusion of fructose into the small intestine of T(3)-injected rats at 21 d induced expression of the GLUT5 gene, but one into that of vehicle-injected rats did not. These results suggest that T(3) and fructose coordinately enhance jejunal expression of the GLUT5 gene in rats during weaning period. 相似文献
109.
Hyojin Park Sungwoon Lee Pravesh Shrestha Jihye Kim Jeong Ae Park Yeongrim Ko Young Ho Ban Dae-Young Park Sang-Jun Ha Gou Young Koh Victor Sukbong Hong Naoki Mochizuki Young-Myeong Kim Weontae Lee Young-Guen Kwon 《The Journal of cell biology》2015,211(3):619-637
The phosphoinositide 3-kinase–Akt signaling pathway is essential to many biological processes, including cell proliferation, survival, metabolism, and angiogenesis, under pathophysiological conditions. Although 3-phosphoinositide–dependent kinase 1 (PDK1) is a primary activator of Akt at the plasma membrane, the optimal activation mechanism remains unclear. We report that adhesion molecule with IgG-like domain 2 (AMIGO2) is a novel scaffold protein that regulates PDK1 membrane localization and Akt activation. Loss of AMIGO2 in endothelial cells (ECs) led to apoptosis and inhibition of angiogenesis with Akt inactivation. Amino acid residues 465–474 in AMIGO2 directly bind to the PDK1 pleckstrin homology domain. A synthetic peptide containing the AMIGO2 465–474 residues abrogated the AMIGO2–PDK1 interaction and Akt activation. Moreover, it effectively suppressed pathological angiogenesis in murine tumor and oxygen-induced retinopathy models. These results demonstrate that AMIGO2 is an important regulator of the PDK1–Akt pathway in ECs and suggest that interference of the PDK1–AMIGO2 interaction might be a novel pharmaceutical target for designing an Akt pathway inhibitor. 相似文献
110.
Reversal of mutualism in a leafflower–leafflower moth association: the possible driving role of a third‐party partner 下载免费PDF全文
Atsushi Kawakita Ko Mochizuki Makoto Kato 《Biological journal of the Linnean Society. Linnean Society of London》2015,116(3):507-518
A major goal in the study of mutualism is to understand how co‐operation is maintained when mutualism may potentially turn into parasitism. Although certain mechanisms facilitate the persistence of mutualism, parasitic species have repeatedly evolved from mutualistic ancestors. However, documented examples of mutualism reversals are still rare. Leafflowers (Phyllantheae; Phyllanthaceae) include approximately 500 species that engage in obligate mutualism with leafflower moths (Epicephala; Gracillariidae), which actively pollinate flowers, and whose larvae feed on the resulting seeds. We found that the Taiwanese population of the Phyllanthus reticulatus species complex was associated with six sympatric Epicephala species, of which three were derived parasites that induced gall formation on flowers/buds and produced no seeds. Notably, two parasitic species have retained mutualistic pollination behaviour, suggesting that the parasitism was likely not selected for to reduce the cost of mutualism. We propose that the galling habit evolved as an adaptation to escape parasitism by a specialized braconid wasp. The tough gall produced by one species was almost free of braconid parasitism, and the swollen gall induced by the other species probably prevents attack as a result of the larger airspace inside the gall. Our findings suggest that the presence of a third‐party partner can greatly influence the evolutionary fate of mutualisms, regardless of whether the pairwise interaction continues to favour co‐operation. 相似文献