全文获取类型
收费全文 | 861篇 |
免费 | 13篇 |
国内免费 | 24篇 |
出版年
2023年 | 9篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 16篇 |
2018年 | 12篇 |
2017年 | 13篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 30篇 |
2013年 | 51篇 |
2012年 | 19篇 |
2011年 | 33篇 |
2010年 | 19篇 |
2009年 | 35篇 |
2008年 | 45篇 |
2007年 | 33篇 |
2006年 | 24篇 |
2005年 | 29篇 |
2004年 | 25篇 |
2003年 | 26篇 |
2002年 | 23篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 20篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 23篇 |
1995年 | 18篇 |
1994年 | 23篇 |
1993年 | 17篇 |
1992年 | 11篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 14篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 26篇 |
1984年 | 22篇 |
1983年 | 8篇 |
1982年 | 13篇 |
1981年 | 22篇 |
1980年 | 9篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 11篇 |
1976年 | 6篇 |
1975年 | 15篇 |
1974年 | 17篇 |
1973年 | 9篇 |
排序方式: 共有898条查询结果,搜索用时 31 毫秒
11.
Birgit Rose Toshihiko Yada Werner R. Loewenstein 《The Journal of membrane biology》1986,94(2):129-142
Summary The viralsrc gene downregulates junctional communication, closing cell-to-cell membrane channels presumably by way of the phosphoinositide signal route. We show that TMB-8 [8-N, N-(diethylamino) octyl-3,4,5-trimethoxybenzoate] counteracts this downregulation in cells transformed by temperature-sensitive mutant Rous sarcoma virus: TMB-8 (36–72 m) raises junctional permeability when applied during activity ofsrc protein kinase, i.e., at steady permissive temperature; and TMB-8 inhibits the fall of junctional permeability, when the activity ofsrc protein kinase gets turned on. TMB-8 also (reversibly) inhibits the growth of the cells at permissive temperature and reverses the morphological changes associated with transformation. The morphological reversal lags several hours behind the junctional-permeability reversal. Communication recovers within a few minutes when the activity of thesrc protein kinase is turned off (in absence of TMB-8). Sodium orthovanadate (20 m) prevents this recovery, but it has no major effect on junctional permeability on its own. We discuss possible modes of action of these agents on critical stages of the signal route, related to intracellular Ca2+ and protein kinase C. 相似文献
12.
S. O. Aisien F. I. Opute S. N. Ali B. A. Obiamiwe 《International journal for parasitology》1986,16(6):655-657
& Obiamiwe B. A. 1986. Lipid composition of adult Foleyella agamae. International Journal for Parasitology 16: 655–657. The lipid and fatty acid composition of the filarial parasite Foleyella agamae were investigated. Total lipids accounted for 7.05% of the parasite fresh weight. Neutral lipids comprised 56.34% of the total and polar lipids 43.66%. The major lipid classes detected include sterol esters, cholesterol, phosphatidyl choline and phosphatidyl ethanolamine. Fatty acids varying in chain length from 10 carbon atoms through 20 carbon atoms were identified in the total lipid extract. The 18 carbon fatty acids formed the predominant components. The 20 carbon fatty acids were confined to the polar lipds. 相似文献
13.
Jila H. Boal Scott F. Deamond Daniel E. Callahan Sarah A. Bruce Paul O. P. Ts'o L. L. Kan 《Cell biochemistry and biophysics》1989,14(3):245-256
The nuclear magnetic resonance (NMR) parameters, spin-lattice (T1), and spin-spin (T2) relaxation time, are usually longer for neoplastic cells than for normal cells of the same cell type. This has generally
been true at low NMR frequencies (≤100 MHz) when comparisons have been made between normal and neoplastic cells that have
both spent a short time in culture. We have previously demonstrated that although the T1 values of paired normal and neoplastic Syrian hamster (SH) fibroblastic cells in culture are not significantly different
when measured at 300 MHz, the 300 MHz T2 values for the neoplastic cells are smaller than those of the normal cells. (Xin et al. (1986),Cell Biophysics
8, 213.) Since treatment of normal diploid cells with polypeptide growth factors or tumor promoters frequently results in reversible
expression of neoplasia-associated phenotypes, T1 and T2 were obtained at 300 MHz for treated and untreated SH cells to see if these compounds could also produce smaller 300 MHz
T2 values. Secondary culture SH fetal fibroblast cells were treated with epidermal growth factor (EGF), fibroblast growth factor
(FGF), phorbol-12,13-didecanoate (PDD) and 4-α-phorbol-12,13-didecanoate (4αPDD). Treatment with either growth factor resulted
in smaller T2 values, but a statistically significant decrease was not observed for PDD or 4αPDD. The observed reductions in T2 values were correlated with the morphological and growth-stimulatory effects of these compounds on the cells. 相似文献
14.
15.
B. E. Slack M. Liscovitch J. K. Blusztajn R. J. Wurtman 《Journal of neurochemistry》1989,53(2):472-481
The phosphatidylserine (PtdSer) content of human cholinergic neuroblastoma (LA-N-2) cells was manipulated by exposing the cells to exogenous PtdSer, and the effects on phospholipid content, membrane composition, and incorporation of choline into phosphatidylcholine (PtdCho) were investigated. The presence of liposomes containing PtdSer (10-130 microM) in the medium caused time- and concentration-dependent increases in the PtdSer content of the cells, and smaller and slower increases in the contents of other membrane phospholipids. The PtdSer levels in plasma membrane and mitochondrial fractions prepared by discontinuous sucrose density gradient centrifugation increased by 50 and 100%, respectively, above those in control cells after 24 h of exposure to PtdSer (130 microM). PtdSer caused a concomitant, concentration-dependent increase of up to twofold in the incorporation of [methyl-14C]choline chloride into PtdCho at a choline concentration (8.5 microM) compatible with activation of the CDP-choline pathway, suggesting that the levels of PtdSer in membranes may serve as a stimulus to regulate overall membrane composition. PtdSer caused a mean increase of 41% in PtdCho labeling, but the phorbol ester, phorbol 12-myristate 13-acetate (PMA), which stimulates PtdCho synthesis in a number of cell lines, increased [14C]PtdCho levels by only 14% in LA-N-2 cells, at a concentration (100 nM) which caused complete translocation of the calcium- and phospholipid-dependent enzyme protein kinase C to the membrane. The translocation was inhibited by prior exposure of the cells to PtdSer. Treatment with PMA for 24 h diminished protein kinase C activity by 80%, but increased the labeling of PtdCho in both untreated and PtdSer-treated cells. These data suggest that uptake of PtdSer by LA-N-2 cells alters both the phospholipid composition of the membrane and synthesis of the major membrane phospholipid PtdCho; the latter effect does not involve activation of protein kinase C. 相似文献
16.
Kaoru Nakamura Takehiko Miyai Kiyoko Inoue Seiji Kawasaki Shinzaburo Oka Atsuyoshi Ohno 《Biocatalysis and Biotransformation》1990,3(1):17-24
Esters of 3-methyl-2-oxobutanoic acid are reduced with bakers' yeast by three methods: free bakers' yeast in water, immobilized bakers' yeast in water, and immobilized bakers' yeast in hexane. Although (R)-hydroxy esters are obtained in all cases, the enantiomeric excess varies from 3% (reduction of the methyl ester with free bakers' yeast in water) to 93% (reduction of the butyl ester with immobilized bakers' yeast in hexane) depending on the structure of substrate and on the reaction conditions. The mechanism of the present stereochemical control is discussed. 相似文献
17.
J.C. Hervé F. Pluciennik F. Verrecchia B. Bastide B. Delage M. Joffre J. Délèze 《The Journal of membrane biology》1996,149(3):179-187
17β-estradiol propionate was found to reduce the gap junctional communication in a concentration range similar to that of
testosterone propionate, in primary cultures of rat Sertoli cells and cardiac myocytes. Uncoupling was reversible on washing
out and occurred without concomitant rise in the intracellular calcium concentration.
Esterification was a prerequisite for the activity of extracellularly applied steroid compounds (for example, testosterone
was ineffective even at external concentrations up to 100 μm, whereas its intracellular application at 1 μm totally interrupted intercellular communication), but their uncoupling efficiency did not depend on the nature of the ester
chain nor on its position on the steroid nucleus. The derivatives of two other androgen hormones (derivatives of the androstane
nucleus) were also efficient as junctional uncouplers. Among five steroid molecules belonging to the pregnane family, only
one (pregnanediol diacetate) interrupted the junctional communication. Neither cholic acid nor cholesteryl acetate or ouabain
showed this effect. Altogether, no correlation with the presence or position of double bonds nor with the trans- or cis-fusion of the A and B rings could be recognized.
These results suggest that this reversible, nondeleterious uncoupling effect of steroids is independent of the shape of the
molecules and is more probably related to their size and liposolubility, that condition their insertion into the lipid bilayer.
Their incorporation into the membrane could disturb the activity of the membrane proteins by a physical mechanism.
Received: 10 April 1995/Revised: 27 October 1995 相似文献
18.
Abstract: To determine whether protein kinase C (PKC) mediates release of peptides from sensory neurons, we examined the effects of altering PKC activity on resting and evoked release of substance P (SP) and calcitonin gene-related peptide (CGRP). Exposing rat sensory neurons in culture to 10 or 50 n M phorbol 12,13-dibutyrate (PDBu) significantly increased SP and CGRP release at least 10-fold above resting levels, whereas the inactive 4α-PDBu analogue at 100 n M had no effect on release. Furthermore, 100 n M bradykinin increased peptide release approximately fivefold. Down-regulation of PKC significantly attenuated the release of peptides evoked by either PDBu or bradykinin. PDBu at 1 n M or 1-oleoyl-2-acetyl- sn -glycerol at 50 µ M did not alter resting release of peptides, but augmented potassium- and capsaicin-stimulated release of both SP and CGRP approximately twofold. This sensitizing action of PKC activators on peptide release was significantly reduced by PKC down-regulation or by pretreating cultures with 10 n M staurosporine. These results establish that activation of PKC is important in the regulation of peptide release from sensory neurons. The PKC-induced enhancement of peptide release may be a mechanism underlying the neuronal sensitization that produces hyperalgesia. 相似文献
19.
Abstract: Previous studies have demonstrated that bovine chromaffin cells cultured in medium with 10 nM insulin-like growth factor-I (IGF-I) secrete about twofold more catecholamine when exposed to secretory stimuli than do cells cultured without IGF-I. The purpose of this study was to determine whether protein kinase C (PKC) is involved in the effect of IGF-I on secretion from these cells. PKC was down-regulated in the cells by 16–18 h of treatment with β-phorbol didecanoate (β-PDD; 100 nM). Such treatment had no effect on high-K+-stimulated secretion from cells cultured without IGF-I; however, secretion from cells cultured with IGF-I was reduced to a level comparable to that in cells cultured without the peptide. The inactive isomer, α-PDD (100 nM), had no effect on secretion from untreated or IGF-I-treated chromaffin cells. The effect of β-PDD was time and concentration dependent, with 100 nM β-PDD producing a maximal effect in 8–10 h. In situ PKC activity measured in permeabilized cells treated with PMA (300 nM) was decreased by~40% by 10 h and was reduced to almost basal levels by 18 h. Immunoblotting experiments demonstrated that both α-and ε-PKC were lost from the cells with time courses similar to that seen in the in situ PKC assay. Overnight treatment with the PKC inhibitor H7 (100 μM) prevented the enhanced secretion normally seen in IGF-l-treated cells, whereas HA1004 had no effect. High-K+-stimulated 45Ca2+ uptake in IGF-I-treated cells was attenuated by long-term treatment with β-PDD (200 nM) or H7 (100 μM). Together these observations suggest that PKC is required for IGF-I-enhanced secretion from chromaffin cells. 相似文献
20.
Maike Petersen Elisabeth Häusler Juliane Meinhard Barbara Karwatzki Claudia Gertlowski 《Plant Cell, Tissue and Organ Culture》1994,38(2-3):171-179
Suspension cultures of Coleus blumei accumulate very high amounts of rosmarinic acid, an ester of caffeic acid and 3,4-dihydroxyphenyllactate, in medium with elevated sucrose concentrations. Since the synthesis of this high level of rosmarinic acid occurs in only five days of the culture period, the activities of the enzymes involved in the biosynthesis are very high. Therefore all the enzymes necessary for the formation of rosmarinic acid from the precursors phenylalanine and tyrosine could be isolated from cell cultures of Coleus blumei: phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase, hydroxycinnamoyl:CoA ligase, tyrosine aminotransferase, hydroxyphenylpyruvate reductase, rosmarinic acid synthase and two microsomal 3- and 3-hydroxylases. The main characteristics of these enzymes of the proposed biosynthetic pathway of rosmarinic acid will be described.Abbreviations DHPL
3,4-dihydroxyphenyllactate
- DHPP
3,4-dihydroxyphenylpyruvate
- pHPL
4-hydroxyphenyllactate
- pHPP
4-hydroxyphenylpyruvate
- RA
rosmarinic acid 相似文献