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1.
Pregnenolone, dehydroepiandrosterone, and their sulfate and fatty acid esters in the rat brain 总被引:6,自引:1,他引:5
The rat brain contains large amounts of pregnenolone (P) and dehydroepiandrosterone (D) arising from local biosynthetic pathways. We have devised a procedure for the measurement of both "neurosteroids" either unconjugated or released from their sulfate (S) or fatty acid (L) esters. The measurements were performed at the acrophase of the circadian variation of neurosteroids, and confirmed the large accumulation of P (25 +/- 8 ng/g, mean +/- SD) and of PS (19 +/- 6 ng/g) and DS (2.1 +/- 0.5 ng/g) in the brain of adult male rats. We found that fatty acid esters constitute the major species of neurosteroids in brain (PL 46 +/- 14, and DL 36 +/- 7 ng/g, in adult males). The levels of P and DS were increased by daily injection of vehicle to intact males, whereas castration, without or with testosterone or estradiol supplementation (2 mg daily for 7 days), did not produce a significant change of neurosteroids concentrations. Measurements of neurosteroids had not been previously reported in cyclic females. The levels of P, PL, and DS were identical in proestrous females and in intact males, whereas PS (26 +/- 6 ng/g) and DL (50 +/- 16 ng/g) were increased in females. Compared to proestrous females, diestrous females had lower levels of PS (19 +/- 6 ng/g), DS (1.7 +/- 0.4 ng/g), and PL (43 +/- 19 ng/g). These differences suggested a modulatory role of ovarian secretions on the metabolism of neurosteroids. 相似文献
2.
Neurosteroids: a new brain function? 总被引:24,自引:0,他引:24
The biosynthesis of neurosteroids proceeds through cholesterol side-chain cleavage, and gives rise to pregnenolone (P) and dehydroepiandrosterone (D). These steroids accumulate in the rat brain independently of the supply by peripheral endocrine glands. This led to the discovery of a steroid biosynthesis pathway in rat brain oligodendrocytes based on enzyme immunocytochemistry and conversion of radioactive precursors to C-21 steroids. Several biological functions have been proposed for P and D. They may serve as precursors of other steroids (such as progesterone and testosterone and their metabolites). They are implicated in the control of some behavioural activities. They have excitatory effects on neurons, and they modulate the function of GABAA-receptors. These observations may apply to all mammalian species including the human, and the physiological significance of neurosteroid synthesis needs further investigation. The relationship between steroids and cerebral function may be reconsidered in the light of a new fact: the existence of a biosynthetic pathway of these compounds from cholesterol, assured in the brain by the oligodendrocytes, glial cells which synthesize myelin. 相似文献
3.
Blood samples were collected from 118 white-tailed deer (Odocoileus virginianus) shot on the Fort Riley Military Installation in northeastern Kansas. Values for these deer for hematocrit, glucose, alkaline phosphatase, uric acid, total protein, albumin, and calcium were within the ranges reported in previous studies for undrugged white-tailed deer. Abnormally high concentrations of serum glutamic oxaloacetate transaminase (SGOT) and lactic dehydrogenase (LDH) were attributed to general trauma and tissue damage caused by shooting the deer. Fawns had higher concentrations of alkaline phosphatase than adults and had lower concentrations in winter than at other times of the year. Serum urea nitrogen (SUN) concentrations fluctuated seasonally. Elevated concentrations of SUN in adult males killed in December were attributed to an increased catabolism of muscle protein caused by low dietary intake and high energy requirements during the rut. Cholesterol concentrations varied seasonally without regard to age or sex. 相似文献
4.
I Jung-Testas F Alliot B Pessac P Robel E E Baulieu 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1989,308(6):165-170
Primary cultures of glial cells from newborn rat forebrain were tested after 3 to 4 weeks. Oligodendrocytes and astrocytes were characterized by immunofluorescence with monoclonal antibodies to galactocerebroside and glial fibrillary acidic protein, respectively. The cytoplasm of oligodendrocytes was specifically and intensely immunostained with monospecific polyclonal antibodies to the cytochrome P-450scc involved in the synthesis of pregnenolone from cholesterol. This observation brings additional support to the concept of "neurosteroids". 相似文献
5.
A single thin layer chromatography and three antibodies were used for the specific radioimmunoassay of four androgens in pooled rat plasma (Sprague-Dawley adult males). The following values were found (pg/ml ± SD). Testosterone : 3, 138 ± 173; dihydrotestosterone : 374 ± 20; 5α-androstane-3α 17β-diol : 284 ± 24; 5α-androstane-3β, 17β-diol : 223 ± 11. 相似文献
6.
7.
Burch ML Osman N Getachew R Al-Aryahi S Poronnik P Zheng W Hill MA Little PJ 《The international journal of biochemistry & cell biology》2012,44(5):722-727
The current paradigm of G protein coupled receptor signaling involves a classical pathway being the activation of phospholipase C and the generation of 1,4,5-inositol trisphosphate, signaling through β-arrestin scaffold molecules and the transactivation of tyrosine kinase growth factor receptors. Transactivation greatly expands the range of signaling pathways and responses attributable to the receptor. Recently it has been revealed that G protein coupled receptor agonists can also transactivate the serine/threonine kinase cell surface receptor for transforming growth factor-β (Alk5). This leads to the generation of carboxyl terminal phosphorylated Smad2 which is the immediate downstream product of the activated Alk5. Thus, the current paradigm of G protein coupled signaling can be expanded to include the transactivation of the serine kinase receptor Alk5. These insights expand the possibilities for outcomes of therapeutically targeting GPCRs where more substantive and prolonged actions such as the synthesis of extracellular matrix may be affected. 相似文献
8.
Jinhong Ren Tina L. Mistry Pin-Chih Su Shahila Mehboob Robel Demissie Leslie Wo-Mei Fung Arun K. Ghosh Michael E. Johnson 《Bioorganic & medicinal chemistry letters》2018,28(11):2074-2079
We have previously reported benzimidazole-based compounds to be potent inhibitors of FabI for Francisella tularensis (FtFabI), making them promising antimicrobial hits. Optically active enantiomers exhibit markedly differing affinities toward FtFabI. The IC50 of benzimidazole (?)-1 is ~100× lower than the (+)-enantiomer, with similar results for the 2 enantiomers. Determining the absolute configuration for these optical compounds and elucidating their binding modes is important for further design. Electronic circular dichroism (ECD) quantum calculations have become important in determining absolute configurations of optical compounds. We determined the absolute configuration of (?)/(+)-1 and (?)/(+)-2 by comparing experimental spectra and theoretical density functional theory (DFT) simulations of ECD spectra at the B3LYP/6-311+G(2d, p) level using Gaussian09. Comparison of experimental and calculated ECD spectra indicates that the S configuration corresponds to the (?)-rotation for both compounds 1 and 2, while the R configuration corresponds to the (+)-rotation. Further, molecular dynamics simulations and MM-GBSA binding energy calculations for these two pairs of enantiomers with FtFabI show much tighter binding MM-GBSA free energies for S-1 and S-2 than for their enantiomers, R-1 and R-2, consistent with the S configuration being the more active one, and with the ECD determination of the S configuration corresponding to (?) and the R configuration corresponding to (+). Thus, our computational studies allow us to assign (?) to (S)- and (+) to (R)- for compounds 1 and 2, and to further evaluate structural changes to improve efficacy. 相似文献
9.
P. Agnellus Schneider Reinhard Hoppe G. Timmermann G. L. Maclean Hans Deetjen H. Deetjen F. Schmitz Detlef Robel Herbert Ringleben Vesta Stresemann Erwin R. Scherner Eckart Schwarze H. Kumerloeve Heinrich Dathe und Wolfgang Fischer 《Journal of Ornithology》1969,110(1):101-112
Zusammenfassung Die Schlußfolgerungen, dieStegmann (J. Orn. 109, 1968, p. 441–445) für die verwandtschaftliche Stellung der Flughühner auf Grund seiner eigenen Untersuchungen und an Hand anderer Quellen zieht, werden kommentiert. Es wird gezeigt, daß einige dieser Schlußfolgerungen nur auf morphologischen Merkmalen beruhen und mit den zu anderen Resultaten gelangten ethologischen und physiologischen Untersuchungsergebnissen nicht zu vereinbaren sind. Außerdem erscheint es unwahrscheinlich, daß die Flughühner, deren Ursprung von bodenlebenden Nestflüchtern unbestritten ist, auf dem Umweg über die baum- und felsbewohnenden nesthockenden Tauben erst sekundär wieder zu bodenbewohnenden Nestflüchtern geworden sind. Es gibt kein einziges Flughuhn-Merkmal, das diese Hypothese stützen könnte. 相似文献
10.
Immunoreactive cytochrome P-450(17 alpha) in rat and guinea-pig gonads, adrenal glands and brain. 总被引:2,自引:0,他引:2
C Le Goascogne N Sananès M Gouézou S Takemori S Kominami E E Baulieu P Robel 《Journal of reproduction and fertility》1991,93(2):609-622
The cytochrome P-450(17 alpha)-hydroxylase, 17----20 lyase (P-450(17 alpha)) is the key enzyme responsible for the biosynthesis of androgens in steroidogenic organs. Its cellular localization has been examined with an immunohistochemical technique. In immature rat ovary, P-450(17 alpha) was first detected in sparse interstitial cells on postnatal Day 8. The number of immunoreactive interstitial cells increased thereafter and the intensity of P-450(17 alpha) staining in these cells was highest at 3 weeks of age. The intensity of staining then started to decline and was very faint at Day 35. From 6 weeks on, the distribution of immunoreactive P-450(17 alpha) was of the adult type: it was detected exclusively in the thecal cells of the large antral, preovulatory, follicles. P-450(17 alpha) was not detectable during pregnancy except on the day of parturition, when thecal cells were transiently immunoreactive. The staining had vanished 24 h after delivery. Human chorionic gonadotrophin (hCG), injected into immature females on Days 24 to 26, induced P-450(17 alpha) prematurely in thecal cells. When injected on Days 12 to 14 of pregnancy, hCG also induced P-450(17 alpha) in the thecal cells surrounding the largest follicles, whereas the interstitial and luteal cells were not immunostained. The antiprogestin RU486, injected on Day 16 of pregnancy, reinstated P-450(17 alpha) (and P-450scc) immunoreactivity in the thecal cells. Oestradiol selectively suppressed P-450(17 alpha) expression in the thecal cells of RU486-treated females. In immature guinea-pig ovary, P-450(17 alpha) was immunostained in thecal cells, not in interstitial cells, although the interstitial cells expressed the delta 5-3 beta-hydroxysteroid dehydrogenase. P-450(17 alpha) was also immunolocalized in the Leydig cells of rat and guinea-pig testes, and in the guinea-pig adrenal cortex (zonae fasciculata and reticularis), but not in the rat adrenal cortex. P-450(17 alpha) was not detectable in the brain of either rat or guinea-pig. 相似文献