全文获取类型
收费全文 | 670篇 |
免费 | 29篇 |
国内免费 | 13篇 |
专业分类
712篇 |
出版年
2023年 | 5篇 |
2022年 | 10篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 10篇 |
2018年 | 21篇 |
2017年 | 11篇 |
2016年 | 11篇 |
2015年 | 19篇 |
2014年 | 40篇 |
2013年 | 57篇 |
2012年 | 22篇 |
2011年 | 42篇 |
2010年 | 21篇 |
2009年 | 21篇 |
2008年 | 20篇 |
2007年 | 36篇 |
2006年 | 24篇 |
2005年 | 32篇 |
2004年 | 20篇 |
2003年 | 17篇 |
2002年 | 15篇 |
2001年 | 12篇 |
2000年 | 18篇 |
1999年 | 14篇 |
1998年 | 8篇 |
1997年 | 18篇 |
1996年 | 9篇 |
1995年 | 17篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 18篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1985年 | 7篇 |
1984年 | 12篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 7篇 |
1973年 | 2篇 |
1972年 | 2篇 |
排序方式: 共有712条查询结果,搜索用时 0 毫秒
1.
This essay attempts to summarize some of the best evidence for the role of inositol trisphosphate as a second messenger in signal transduction processes. The following aspects are addressed in the essay: (a) The synthesis of inositol trisphosphate and other inositol lipids, (b) Receptor-phosphatidylinositol bisphosphate phospholipase C coupling and the N-ras protooncogene, (c) Inositol trisphosphate and intracellular calcium, (d) Cell growth and oncogenes, (e) Receptors linked to the phosphatidylinositol cycle, (f) Phototransduction and (g) Interactions between inositol trisphosphate and other second messengers.Abbreviations Cyclic AMP
Adenosine 3,5-cyclic monophosphate
- Cyclic GMP
Guanosine 3,5-cyclic monophosphate
- DG
sn, 1,2-Diacylglycerol
- EGF
Epidermal growth factor
- GDP
Guanosine diphosphate
- GTP
Guanosine triphosphate
- IP
Inositol 1-monophosphate
- IP2
Inositol 1,4-diphosphate
- IP3
Inositol 1,4,5-trisphosphate
- PA
Phosphatidic acid
- PDGF
Platelet-derived growth factor
- PI
Phosphatidylinositol
- PIP
Phosphatidylinositol 4-monophosphate
- PIP2
Phosphatidylinositol 4,5-bisphosphate
- PIP3
Phosphatidylinositol 3,4,5-trisphosphate
- PLC
Phospholipase C 相似文献
2.
3.
Mark Phillippe Trevania Saunders Shrikar Bangalore 《In vitro cellular & developmental biology. Plant》1990,26(4):369-378
Summary The following studies were undertaken to develop a cultured uterine myocyte model which would allow further clarification
of the adrenergic signal transduction mechanisms utilized by these myocytes. After mechanical removal of the endometrium,
rabbit uterine myoctes were isolated by an overnight enzymatic disaggregation using collagenase and DNase I. The isolated
myocytes were maintained in culture in 75-cm2 flasks containing Waymouth's MB 751/1 medium-10% fetal bovine serum along with 10−8
M estradiol, penicillin, streptomycin, and Fungizone. The phase contrast and electron micrographic appearance of these cells
was consistent with that previously reported for smooth muscle myocytes in culture. Immunocytochemical studies utilizing monoclonal
anti-alpha-smooth muscle actin antibodies confirmed the presence of smooth muscle actin in these cultured myocytes. Western
blot studies similarly confirmed the presence of alpha-smooth muscle actin in rabbit myometrial tissue and the cultured myocytes,
both the primary and F1 generation. After prelabeling the myocytes with [3H]inositol, adrenergic stimulation experiments demonstrated alpha-1 receptor mediated stimulation of inositol phosphates.
Beta receptor stimulation experiments confirmed cAMP production in these cultured myocytes, and the ability of clonidine,
an alpha-2 agonist, to inhibit forskolin stimulated cAMP production confirmed the presence of functional alpha-2 adrenergic
receptors in these myocytes. In conclusion, these cultured rabbit uterine myocytes have provided an in vitro model which can
be utilized to further clarify the adrenergic receptor signal transduction mechanisms in genital tract smooth muscle.
This research was supported by grant HD-22063 from the National Institutes of Health, Bethesda, MD. 相似文献
4.
1α,25-Dihydroxyvitamin D3 (1α, 25-(OH)2D3) has been shown to increase cytosolic calcium and inositol trophosphate levels in rat osteosarcoma cells (ROS 17/2.8) and to increase nuclear calcium in these cells. To determine the mechanism(s) of 1α, (OH)2D3-induced changes in the calcium, the effect of the hormone on phospholipid metabolism in isolated osteoblast nuclei wa assessed. 1α,25 (OH)2D3, 20 nM, increased inositol triphosphate levels in the nuclei after 5 min of treatment. The biologically inactive epimer, 1β,25-(OH)2D3, had no significant effect on inositol triphosphate levels. ATP, 1 mM, also increased inositol triphosphate levels in the isolated nuclei after 5 min. 1α,25-(OH)2D3, 20 nM, increased calcium in the isolated nuclei in the presence but not in the absence of extranuclear calcium with 5 min. Nuclear calcium was also increased within 5 min by ATP, 1 mM, and inositol triphosphate, 1 mM. The effects of ATP on nuclear calcium was not additive with 1α, 25-(OH)2D3, suggesting that these two agents increase nuclear calcium in these osteoblast-like cells by similar mechanisms. In summary, 1α,25-(OH)2D3 amd ATP rapidly increase inositol triphosphate levels in isolated from ROS 17/2.8 cells. The hormone, the nucleotide, and the inositol phospholipid nuclear calcium. Thus, the 1α,25-(OH)2D3 and ATP effects of nuclear calcium may be mediated by changes in phospholipid metabolism in the nuclei of these osteoblastlike cells. © Wiley-Liss, Inc. 相似文献
5.
Shigenobu Kanba Nobuyuki Sasakawa Toshio Nakaki Kiyoko-Shimizu Kanba Gohei Yagi Ryuichi Kato Elliott Richelson 《Journal of neurochemistry》1991,57(6):2011-2015
Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). PGE1 transiently increased inositol 1,4,5-trisphosphate formation, peaking at 20 s. There was more than a 10-fold difference between the ED50 for PGE1 at cyclic AMP formation (70 nM) and its ED50 values at IP accumulation (1 microM), cyclic GMP formation (2 microM), and [Ca2+]i increase (5 microM). PGE1-mediated IP accumulation, cyclic GMP formation, and [Ca2+]i increase depended on both the concentration of PGE1 and extracellular calcium ions. PGE1 had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE2, PGF2 alpha, or PGD2. A protein kinase C activator, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, had opposite effects on PGE1-mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). These data suggest that there may be subtypes of the PGE1 receptor in this clone: a high-affinity receptor mediating cyclic AMP formation, and a low-affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization. 相似文献
6.
Xiaokong Gao Caden G. Bonzerato Richard J.H. Wojcikiewicz 《The Journal of biological chemistry》2022,298(6)
Long-term activation of inositol 1,4,5-trisphosphate receptors (IP3Rs) leads to their degradation by the ubiquitin–proteasome pathway. The first and rate-limiting step in this process is thought to be the association of conformationally active IP3Rs with the erlin1/2 complex, an endoplasmic reticulum–located oligomer of erlin1 and erlin2 that recruits the E3 ubiquitin ligase RNF170, but the molecular determinants of this interaction remain unknown. Here, through mutation of IP3R1, we show that the erlin1/2 complex interacts with the IP3R1 intralumenal loop 3 (IL3), the loop between transmembrane (TM) helices 5 and 6, and in particular, with a region close to TM5, since mutation of amino acids D-2471 and R-2472 can specifically block erlin1/2 complex association. Surprisingly, we found that additional mutations in IL3 immediately adjacent to TM5 (e.g., D2465N) almost completely abolish IP3R1 Ca2+ channel activity, indicating that the integrity of this region is critical to IP3R1 function. Finally, we demonstrate that inhibition of the ubiquitin-activating enzyme UBE1 by the small-molecule inhibitor TAK-243 completely blocked IP3R1 ubiquitination and degradation without altering erlin1/2 complex association, confirming that association of the erlin1/2 complex is the primary event that initiates IP3R1 processing and that IP3R1 ubiquitination mediates IP3R1 degradation. Overall, these data localize the erlin1/2 complex–binding site on IP3R1 to IL3 and show that the region immediately adjacent to TM5 is key to the events that facilitate channel opening. 相似文献
7.
Mark Terasaki 《Experimental cell research》2010,316(16):2654-2663
The maturation hormone 1-methyladenine (1-MA) causes meiotic resumption of prophase arrested immature starfish oocytes. Continuous exposure to ≥ 0.5 µM 1-MA causes germinal vesicle breakdown (GVBD) in ∼ 20 min, but oocytes pretreated for > 30 min with a subthreshold dose of 1-MA undergo GVBD much faster (∼ 10 min) when they are exposed to 1 µM 1-MA. Furthermore, a very low subthreshold 1-MA suffices to start the maturation process: oocytes exposed to 0.005 µM 1-MA for up to 10 min followed by 1 µM 1-MA is equivalent to continuous exposure to 1 µM 1-MA. These dose and timing relationships indicate that there is a two-stage dependence on 1-MA. A possible explanation for this dependence is that there are two processes involved: an initial process that is triggered by a low dose of 1-MA, and a second process that cannot start until the first process is completed and is stimulated by a higher dose of 1-MA. These subthreshold 1-MA effects on GVBD timing are not directly coupled to changes in calcium physiology that also occur during maturation. Subthreshold 1-MA was found to cause a transient accumulation of Cdc2/cyclin B into the nucleus. The two-stage dependence indicates that there are unsuspected features in this well-studied pathway leading to GVBD. In the animal, this hormone dependence may help to synchronize maturation throughout all parts of the ovary. 相似文献
8.
Grace Y. Sun Meena Navidi Fu-Gen Yoa Teng-Nan Lin Oliver E. Orth Evan B. Stubbs Jr. Ronald A. MacQuarrie 《Journal of neurochemistry》1992,58(1):290-297
Administration of lithium chloride to rats injected intracerebrally with [3H]inositol led to time- and dose-dependent increases in levels of labeled inositol monophosphates in brain. Quantitative analysis of the inositol phosphates by ion chromatography revealed 37- and 20-fold increases in the mass of myo-inositol 1-phosphate and 4-phosphate, respectively, at 4 h intraperitoneal after injections of 6 mEq/kg of lithium chloride. Albeit to a much lesser extent, lithium administration also resulted in an increase in the level of myo-inositol, 1,4-bisphosphate in brain. The lithium-induced increase in content of labeled inositol monophosphates was marked by a concomitant decrease in content of labeled inositol, and after injections of high doses of lithium, e.g., 10 mEq/kg, this was followed by a general decrease in labeling of the inositol phospholipids. In general, animals injected with [3H]inositol but not lithium did not reveal obvious differences in labeling of inositol monophosphates on stimulation by mecamylamine or pilocarpine. However, when animals were injected with [3H]inositol and then lithium, there were large increases in the levels of labeled inositol monophosphates on administration of these compounds. Administration of atropine to the lithium-treated mice led to a partial reduction in the amount of labeled inositol monophosphates accumulated due to the administration of lithium alone. Furthermore, atropine was able to block the pilocarpine-induced increase in level of labeled inositol monophosphates. These results demonstrate the suitable use of the radiotracer technique together with lithium administration for assessing the effects of drugs and receptor agonists on the signaling system involving polyphosphoinositide turnover in brain. 相似文献
9.
Biomass production,total protein,chlorophylls, lipids and fatty acids of freshwater green and blue-green algae under different nitrogen regimes 总被引:1,自引:0,他引:1
Two green algae (Chlorella vulgaris and Scenedesmus obliquus) and four blue-green algae (Anacystis nidulans, Microcystis aeruginosa, Oscillatoria rubescens and Spirulina platensis) were grown in 81 batch cultures at different nitrogen levels. In all the algae increasing N levels led to an increase in the biomass (from 8 to 450 mg/l), in protein content (from 8 to 54 %) and in chlorophyll. At low N levels, the green algae contained a high percentage of total lipids (45 % of the biomass). More than 70 % of these were neutral lipids such as triacylglycerols (containing mainly 16:0 and 18:1 fatty acids) and trace amounts of hydrocarbons. At high N levels, the percentage of total lipids dropped to about 20 % of the dry weight. In the latter case the predominant lipids were polar lipids containing polyunsaturated C16 and C18 fatty acids. The blue-green algae, however, did not show any significant changes in their fatty acid and lipid compositions, when the nitrogen concentrations in the nutrient medium were varied. Thus the green but not the blue-green algae can be manipulated in mass cultures to yield a biomass with desired fatty acid and lipid compositions. The data may indicate a hitherto unrecognized distinction between prokaryotic and eukaryotic organisms. 相似文献
10.
myo-Inositol monophosphate phosphatase (IMPase) has been purified 888-fold to apparent homogeneity from procine brains. The purification procedure involves: homogenization, ammonium sulfate fractionation, and a number of ion-exchange and gel-filtration chromatography steps. The purified enzyme exhibited a final specific activity of 932 nmol . min(-1) . mg(-1). The molecular mass of the enzyme was estimated to be 29kDa by SDS poly-acrylamide gel electrophoresis and 58 +/- 5 kDa by HPLC gel filtration in 10mM Tris-HCI, pH 7.4. Kinetic measurements have shown that the apparent K(m) value of the phosphatase for the utilization of inositol-1-phosphate and beta-glycerol phosphate are 3.20 x 10(-4) and 8 x 10(-3) M, respectively. Similar to the same enzyme isolated from bovine brains, the porcine brain enzyme has been shown to be inhibited by lithium. The K(1) was determined to be 6.38 x 10(-4) M and the inhibition is uncompetitive. (c) 1995 John Wiley & Sons, Inc. 相似文献