全文获取类型
收费全文 | 1263篇 |
免费 | 67篇 |
专业分类
1330篇 |
出版年
2022年 | 7篇 |
2021年 | 16篇 |
2020年 | 7篇 |
2019年 | 4篇 |
2018年 | 9篇 |
2017年 | 15篇 |
2016年 | 23篇 |
2015年 | 37篇 |
2014年 | 37篇 |
2013年 | 84篇 |
2012年 | 59篇 |
2011年 | 72篇 |
2010年 | 48篇 |
2009年 | 60篇 |
2008年 | 83篇 |
2007年 | 95篇 |
2006年 | 85篇 |
2005年 | 92篇 |
2004年 | 95篇 |
2003年 | 96篇 |
2002年 | 81篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1998年 | 12篇 |
1997年 | 12篇 |
1996年 | 6篇 |
1995年 | 11篇 |
1994年 | 19篇 |
1993年 | 15篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 8篇 |
1975年 | 7篇 |
1974年 | 3篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 4篇 |
1969年 | 3篇 |
排序方式: 共有1330条查询结果,搜索用时 15 毫秒
191.
We examined the effects of supernatants of culture media of MDA-MB-231 and MCF-7 cells on the expression of adhesion molecules on human lymphatic endothelial cells (LECs) and evaluated whether the overexpression of adhesion molecules facilitated the attachment of carcinoma cells to LECs. The 48-h stimulation of MDA-MB-231, but not MCF-7, supernatant produced a significant expression of ICAM-1 on human LECs but little or no expression of E-selectin. Chemical treatment with dialyzed substances of <1,000 molecular weight (MW) caused a complete reduction of the supernatant-mediated response. In contrast, pretreatment with heating, digestion with protease, or chemical treatment with dialyzed substances of <500 MW produced no significant effect on the supernatant-mediated response. ATP (10(-7) M) caused overexpression of ICAM-1 on human LECs similar to that produced by the supernatant of MDA-MB-231. The ATP- and MDA-MB-231 supernatant-mediated responses were significantly reduced by treatment with 10(-6) M suramin (a purinergic P2X and P2Y receptor antagonist). In attachment assays, 10(-7) M ATP or MDA-MB-231 supernatant produced a significant increase in the attachment of carcinoma cells to human LECs. The treatment with 10(-6) M suramin caused a significant reduction of ATP- and supernatant-mediated facilitation of the attachment responses. Additional treatment with anti-ICAM-1 antibody also caused a significant reduction of ATP- and supernatant-mediated facilitation of the attachment responses. The experimental findings suggest that MDA-MB-231 may release or leak ATP, which produces the overexpression of ICAM-1 on human LECs through activation of purinergic P2X and/or P2Y receptors and then facilitates ICAM-1-mediated attachment of carcinoma cells to LECs. 相似文献
192.
Yoshiko Inoue Nao Niwa Taro Mito Hideyo Ohuchi Hidefumi Yoshioka Sumihare Noji 《Mechanisms of development》2002,110(1-2):245-248
We observed expression patterns of hedgehog (hh), wingless (wg), and decapentaplegic (dpp) during gut development of Gryllus bimaculatus (the cricket), a typical hemimetabolous insect, and compared with those observed in Drosophila, a typical holometabolous insect. Gryllus hh(Gbhh) and Gbwg are expressed in both foregut and hindgut, while Gbdpp is expressed only in the hindgut: at the boundaries between the small and large intestine, and between the large intestine and rectum. Although the expression patterns of Gbhh and Gbwg are essentially comparable to those observed in Drosophila, the expression pattern of Gbdpp differs from those of the Drosophila dpp. 相似文献
193.
The Mg2+ ion-assisted activation mechanism of the active site Tyr8 of a human hematopoietic prostaglandin D2 synthase (H-PGDS) was studied by ultraviolet resonance Raman (UVRR) spectroscopy. Addition of Mg2+ to the native H-PGDS at pH 8.0 resulted in the Y8a Raman band of Tyr8 shifting from 1615 cm−1 to 1600 cm−1. This large shift to lower energy of the tyrosine Y8a vibrational mode is caused by the deprotonation of the tyrosine phenol group promoted by binding of Mg2+. Upon subsequent addition of glutathione (GSH), the Mg2+/H-PGDS solution showed the Tyr8 Raman band shifted to 1611 cm−1, which is 11 cm−1 higher than the frequency of the Mg2+ complex of H-PGDS, but 4 cm−1 lower than the Mg2+ free enzyme. These UVRR observations suggest that the deprotonated Tyr8 in the presence of Mg2+ is re-protonated by the abstraction of H+ from the thiol group of GSH, and that the re-protonated Tyr8 species forms a hydrogen bond with the thiolate anion of GSH. Density functional theory calculations on several model complexes of p-cresol were also performed, which suggested that the pKa and vibrational frequencies of the Tyr8 phenol group are affected by the degree and structure of hydration of the Tyr8 residue. 相似文献
194.
Satoru Arata Tohru Hirayama Yuri Akiyama Jun-ichi Mashimo Nobuhiko Kasai Katsuhiko Yoshida Yoshiko Nakamura Yoshio Aoki 《FEMS microbiology letters》1989,60(2):223-225
Abstract In vitro antigenic reactivity of lipid A from Pseudomonas diminuta and Pseudomonas vesicularis with homologous and heterologous lipid A antibodies including monoclonal antibodies was studied by inhibition test of enzyme-linked immunosorbent assay (ELISA). The results suggest that both Pseudomonas lipid As have very similar epitopes, including species-specific and cross-reactive epitopes as compared with enterobacterial lipid A. 相似文献
195.
Kazunori Tanaka Takuya Kanno Yoshiko Yanagisawa Kaori Yasutake Satoshi Inoue Noriaki Hirayama Joh-E Ikeda 《PloS one》2014,9(1)
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron degenerative disease. Given that oxidative stress and resulting chronic neuronal inflammation are thought to be central pathogenic, anti-oxidative agents and modulators of neuronal inflammation could be potential therapies for ALS. We report here that the novel small molecular compound, 2-[mesityl(methyl)amino]-N-[4-(pyridin-2-yl)-1H-imidazol-2-yl] acetamide trihydrochloride (WN1316) selectively suppresses oxidative stress-induced cell death and neuronal inflammation in the late-stage ALS mice. WN1316 has high blood-brain-barrier permeability and water solubility, and boosts both neuronal apoptosis inhibitory protein (NAIP) and NF-E2-related factor 2 (Nrf2) which governed glutathione (GSH)-related anti-oxidation pathway protecting motor neurons against oxidative injuries. Post-onset oral administration of low dose (1–100 µg/kg/day) WN1316 in ALS(SOD1H46R) and ALS(SOD1G93A) mice resulted in sustained improved motor function and post onset survival rate. Immunohistochemical analysis revealed less DNA oxidative damage and motor neuronal inflammation as well as repression of both microgliosis and astrocytosis, concomitant down regulation of interleukin-1β and inducible nitric oxide synthase, and preservation of the motoneurons in anterior horn of lumbar spinal cord and skeletal muscle (quadriceps femoris). Thus, WN1316 would be a novel therapeutic agent for ALS. 相似文献
196.
197.
Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis 下载免费PDF全文
Kazuhiro Nakamura Yoshiko Nakamura 《BioEssays : news and reviews in molecular, cellular and developmental biology》2018,40(8)
The recent discovery of the medullary circuit driving “hunger responses” – reduced thermogenesis and promoted feeding – has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin‐mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. 相似文献
198.
Minami Yoshiko; Takao Hiroyasu; Kanafuji Takeo; Miura Kazuo; Kondo Maki; Hara-Nishimura Ikuko; Nishimura Mikio; Matsubara Hiroshi 《Plant & cell physiology》1997,38(9):1069-1074
rß-Glucosidase of indigo plant (Polygonum tinctorium)has a high substrate specificity for indican (indoxyl rß-D-gIu-coside).To examine the localization of this rß-glucosidase,we fractionated the cells of the leaves and analysed them im-munocytochemically.Immunoelectron micrographs with specific antibodies againstthe rßglucosidase clearly showed that the rß-glucosidasewas localized in the stroma of the chloroplasts in mesophyllcells, but not in the thylakoid membrane. Chloroplasts wereisolated from the crude ho-mogenate of the fresh leaves by Percolldensity gradient centrifugation and then subjected to suborganellarfrac-tionation. rßGlucosidase activity was specificallydetected in the stromal fraction, but not in the thylakoid membrane.This was also supported by the result of an immunoblot of thefractions with anti-rßglucosidase antibodies. Therß-gIu-cosidase was immunocytochemically localizedin the chloroplasts of mesophyll cells, but not in any chloroplastsin marginal cells of the vascular bundle or epidermal cells;ribulose 1,5-bisphosphate carboxylase (Rubisco), a typical stromalprotein, was observed in all chloroplasts in these cells. Theseresults suggest that rß-glucosidase is tissue specificin its expression in the leaves of the indigo plant. (Received April 14, 1997; Accepted July 10, 1997) 相似文献
199.
Yoshiko Iida Keiko Sawabe Masayo Kojima Kazuya Oguro Nobuo Nakanishi Hiroyuki Hasegawa 《European journal of biochemistry》2002,269(19):4780-4788
We previously demonstrated in mast cell lines RBL2H3 and FMA3 that tryptophan hydroxylase (TPH) undergoes very fast turnover driven by 26S-proteasomes [Kojima, M., Oguro, K., Sawabe, K., Iida, Y., Ikeda, R., Yamashita, A., Nakanishi, N. & Hasegawa, H. (2000) J. Biochem (Tokyo) 2000, 127, 121-127]. In the present study, we have examined an involvement of TPH phosphorylation in the rapid turnover, using non-neural TPH. The proteasome-driven degradation of TPH in living cells was accelerated by okadaic acid, a protein phosphatase inhibitor. Incorporation of 32P into a 53-kDa protein, which was judged to be TPH based on autoradiography and Western blot analysis using anti-TPH serum and purified TPH as the size marker, was observed in FMA3 cells only in the presence of both okadaic acid and MG132, inhibitors of protein phosphatase and proteasome, respectively. In a cell-free proteasome system constituted mainly of RBL2H3 cell extracts, degradation of exogenous TPH isolated from mastocytoma P-815 cells was inhibited by protein kinase inhibitors KN-62 and K252a but not by H89. Consistent with the inhibitor specificity, the same TPH was phosphorylated by exogenous Ca2+/calmodulin-dependent protein kinase II in the presence of Ca2+ and calmodulin but not by protein kinase A (catalytic subunit). TPH protein thus phosphorylated by Ca2+/calmodulin-dependent protein kinase II was digested more rapidly in the cell-free proteasome system than was the nonphosphorylated enzyme. These results indicated that the phosphorylation of TPH was a prerequisite for proteasome-driven TPH degradation. 相似文献
200.
An unusual amino acid occurring in the fruiting bodies of Lyophyllum ulmarium was identified as ds-erythro- 2-amino-3,4-dihydroxybutanoic acid, which is a compound found for the first time in biological materials. 相似文献