全文获取类型
收费全文 | 3459篇 |
免费 | 155篇 |
国内免费 | 188篇 |
出版年
2023年 | 28篇 |
2022年 | 29篇 |
2021年 | 53篇 |
2020年 | 65篇 |
2019年 | 73篇 |
2018年 | 81篇 |
2017年 | 61篇 |
2016年 | 63篇 |
2015年 | 88篇 |
2014年 | 139篇 |
2013年 | 174篇 |
2012年 | 84篇 |
2011年 | 132篇 |
2010年 | 99篇 |
2009年 | 144篇 |
2008年 | 190篇 |
2007年 | 176篇 |
2006年 | 138篇 |
2005年 | 129篇 |
2004年 | 122篇 |
2003年 | 97篇 |
2002年 | 103篇 |
2001年 | 84篇 |
2000年 | 85篇 |
1999年 | 78篇 |
1998年 | 74篇 |
1997年 | 81篇 |
1996年 | 70篇 |
1995年 | 95篇 |
1994年 | 75篇 |
1993年 | 87篇 |
1992年 | 78篇 |
1991年 | 81篇 |
1990年 | 71篇 |
1989年 | 87篇 |
1988年 | 62篇 |
1987年 | 63篇 |
1986年 | 48篇 |
1985年 | 52篇 |
1984年 | 48篇 |
1983年 | 53篇 |
1982年 | 62篇 |
1981年 | 29篇 |
1980年 | 22篇 |
1979年 | 21篇 |
1978年 | 10篇 |
1977年 | 7篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1971年 | 2篇 |
排序方式: 共有3802条查询结果,搜索用时 286 毫秒
991.
992.
Enhanced taurine release in cultured cerebellar granule cells in cell-damaging conditions 总被引:2,自引:0,他引:2
Summary The release of taurine from cultured cerebellar granule neurons was studied in different cell-damaging conditions, including hypoxia, hypoglycemia, ischemia, oxidative stress and in the presence of free radicals. The effects of both ionotropic and metabotropic glutamate receptor agonists on the release were likewise investigated. The release of [3H]taurine from the glutamatergic granule cells was increased by K+ (50mM) and veratridine (0.1 mM), the effect of veratridine being the greater. Hypoxia and ischemia produced an initial increase in release compared to normoxia but resulted in a diminished response to K. Hypoglycemia, oxidative stress and free radicals enhanced taurine release, and subsequent K– treatment exhibited a correspondingly greater stimulation. A common feature of taurine release in all the bove conditions was a slow response to the stimulus evoked by K+ and particularly to that evoked by veratridine. All ionotropic glutamate receptor agonists potentiated taurine release, but only the action of kainate seemed to be receptor-mediated. Metabotropic receptor agonists of group I slightly stimulated the release. The prolonged taurine release seen in both normoxia and cell-damaging conditions may be of importance in maintaining homeostasis in the cerebellum and reducing excitability for a longer period than other neuroprotective mechanisms.Abbreviations AIDA
(RS)-1-aminoindan-1,5-dicarboxylate
- AMPA
2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate
- CNOX
6-cyano-7-nitroquinoxaline-2,3-dione
- DCG IV
(2S,2R,3R)-2-(2,3-dicarboxycyclo-propyl)glycine
- DHPG
(S)-3,5-dihydroxyphenylglycine
- EGLU
(2S)-2-ethylglutamate
- L-AP3
L(+)-2-amino-3-phosphonopropionate
- L-AP4
L(+)-2-amino-4-phosphonobutyrate
- L-SOP
o-phospho-l-serine
- NBOX
6-nitro-7-sulphamoyl[f]quinoxaline-2,3-dione
- NMDA
n-methyl-d-aspartate
-
trans-ACPD
(1S,3S)-1-aminocyclopentane-1,3-dicarboxylate 相似文献
993.
Stern MD Song LS Cheng H Sham JS Yang HT Boheler KR Ríos E 《The Journal of general physiology》1999,113(3):469-489
In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium- induced calcium release through ryanodine receptors (RyRs), which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation-contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation-contraction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution. 相似文献
994.
Anoxia-induced dopamine release from rat striatal slices: involvement of reverse transport mechanism 总被引:3,自引:0,他引:3
Incubation of rat striatal slices in the absence of oxygen (anoxia), glucose (aglycemia), or oxygen plus glucose (ischemia) caused significant increases in dopamine (DA) release. Whereas anoxia decreased extracellular 3,4-dihydroxyphenylacetic acid levels by 50%, aglycemia doubled it, and ischemia returned this aglycemia-induced enhancement to its control level. Although nomifensine, a DA uptake blocker, completely protected the slices against anoxia-induced DA depletion, aglycemia- and ischemia-induced increases were not altered. Moreover, hypothermia differentially affected DA release stimulated by anoxia, aglycemia, and ischemia. Involvement of glutamate in DA release induced by each experimental condition was tested by using MK-801 and also by comparing the glutamate-induced DA release with that during anoxia, aglycemia, or ischemia. MK-801 decreased the anoxia-induced DA depletion in a dose-dependent manner. This treatment, however, showed a partial protection in aglycemic conditions but failed to improve ischemia-induced DA depletion. Like anoxia, DA release induced by exogenous glutamate was also sensitive to nomifensine and hypothermia. These results indicate that anoxia enhances DA release by a mechanism involving both the reversed DA transporter and endogenous glutamate. Partial or complete lack of effect of nomifensine, hypothermia, or MK-801 in the absence of glucose or oxygen plus glucose also suggests that experimental conditions, such as the degree of anoxia/ischemia, may alter the mechanism(s) involved in DA depletion. 相似文献
995.
1. Spinal cord ischemia evoked a biphasic increase in CSF-Glu during 20 min of ischemia (40%) and at 2 hr after reperfusion (70%) in the nontreated group that was attenuated by all treated groups. But MK-801(15 g i.t.) did not affect the increased Glu at 2 hr (80%).2. The argyrophilia observed in laminae II–V at 8 hr after reperfusion was attenuated by hypothermia (33°C) and combination with MK-801, but the attenuation was less with MK-801.3. Mild hypothermia attenuated the biphasic increase in CSF-Glu and corresponding development of neuronal damage after spinal cord ischemia.4. Mild hypothermia with NMDA antagonism did not yield any further effects, suggesting that hypothermia itself plays a pivotal role in the protection. 相似文献
996.
Study of the redox properties of metallothionein in vitro by reacting with DsbA protein 总被引:2,自引:0,他引:2
Mammalian metallothionein (MT) contains 20 cysteine residues involved in the two metal clusters without a disulfide bond. The redox reaction of the Cys thiols was proposed to be associated with the metal distribution of MT. The E. coli DsbA protein is extremely active in facilitating thiol/disulfide exchange both in vivo and in vitro. To further investigate the redox properties of MT, reaction between MT and DsbA was carried out in vitro by fluorescence detection. Equilibrium characterization indicates that the reaction is stoichiometric (1:1) under certain conditions. Kinetic study gives a rate constant of the redox reaction of 4.42 × 105 sec–1 M–1, which is 103-fold larger than that of glutathione reacting with DsbA. Metal-free MT (apo-MT) shows a higher equilibrium reduction potential than MT, but exhibits an indistinguishable kinetic rate. Oxidation of MT by DsbA leads to metal release from the clusters. The characteristic fluorescence increase during reduction of DsbA may provide a sensitive probe for exploring the redox properties of some reductants of biological interest. The result also implies that oxidation of Cys thiols may influence the metal release or delivery from MT. 相似文献
997.
Sugita Kenji Mörk Ann-Christin Zhang Guo H. Martinez J. Ricardo 《Molecular and cellular biochemistry》1999,198(1-2):39-46
The expression of protein kinase C (PKC) isoforms and the modulation of Ca2+ mobilization by PKC were investigated in the human submandibular duct cell line A253. Three new PKC (nPKC) isoforms (, , and ) and one atypical PKC (aPKC) isoform () are expressed in this cell line. No classical PKC (cPKC) isoforms were present. The effects of the PKC activator phorbol 12-myristate-13-acetate (PMA) and of the PKC inhibitors calphostin C (CC) and bisindolymaleimide I (BSM) on inositol 1,4,5-trisphosphate (IP3) and Ca2+ responses to ATP and to thapsigargin (TG) were investigated. Pre-exposure to PMA inhibited IP3 formation, Ca2+ release and Ca2+ influx in response to ATP. Pre-exposure to CC or BSM slightly enhanced IP3 formation but inhibited the Ca2+ release and the Ca2+ influx induced by ATP. In contrast, pre-exposure to PMA did not modify the Ca2+ release induced by TG, but reduced the influx of Ca2+ seen in the presence of this Ca2+-ATPase inhibitor. These results suggest that PKC modulates elements of the IP3/Ca2+ signal transduction pathway in A253 cells by (1) inhibiting phosphatidylinositol turnover and altering the sensitivity of the Ca2+ channels to IP3, (2) altering the activity, the sensitivity to inhibitors, or the distribution of the TG-sensitive Ca2+ ATPase, and (3) modulating Ca2+ entry pathways. 相似文献
998.
Cano Georgina Arcaya José Luís Gómez Gerber Maixner William Suarez-Roca Heberto 《Neurochemical research》1999,24(10):1203-1207
Morphine produces a multiphasic modulation of K+-evoked substance P release from trigeminal slices and dorsal root ganglion neurons in culture. We now found that the C-fiber stimulant, capsaicin (1 M), evoked release of substance P that was inhibited, enhanced and inhibited by 0.1 nM, 1 M, and 10 M morphine, respectively. This morphine's multiphasic effect was blocked by naloxone (100 nM). Neonatal treatment with capsaicin produced thermal hypoalgesia and abolished the multiphasic effect of morphine on substance P release evoked by 50 mM K+. These findings suggest that the multiphasic modulation of substance P release by morphine is dependent on C-type afferents and may be of relevance to nociception. 相似文献
999.
Several "soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor" (SNARE) proteins have been identified in rat parotid acinar cells, including VAMP-2, syntaxin 4, and SNAP-23. Furthermore, an association between Munc18c (Munc18-3) and syntaxin 4 has been reported. However, the role of Munc18-3 in secretory granule exocytosis on parotid acinar cells remains unclear. In the present study, we investigated the role of Munc18-3 in rat parotid acinar cells. Munc18-3 was localized on the apical plasma membrane where exocytosis occurs and interacted with syntaxin 4. Anti-Munc18-3 antibody dose-dependently decreased isoproterenol (IPR)-induced amylase release from SLO-permeabilized parotid acinar cells. Furthermore, stimulation of the acinar cells with IPR induced translocation of Munc18-3 from the plasma membrane to the cytosol. Munc-18-3 was not phosphorylated by a catalytic subunit of protein kinase (PK) A but phosphorylated by PKC. Treatment of the plasma membrane with PKC but not PKA induced displacement of Munc18-3 from the membrane. The results indicate that Munc18-3 regulates exocytosis in the acinar cells for IPR-induced amylase release and that phosphorylation of Munc18-3 by PKA is not involved in the mechanism. 相似文献
1000.
Identification and subcellular distribution of endogenous Ins(1,4,5)P(3) 3-kinase B in mouse tissues
Hascakova-Bartova R Pouillon V Dewaste V Moreau C Jacques C Banting G Schurmans S Erneux C 《Biochemical and biophysical research communications》2004,323(3):920-925
Inositol 1,4,5-trisphosphate 3-kinase (IP(3)-3K) catalyses the phosphorylation of inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate. cDNAs encoding three mammalian isoforms have been reported and referred to as IP(3)-3KA, IP(3)-3KB, and IP(3)-3KC. IP(3)-3KB is particularly sensitive to proteolysis at the N-terminus, a mechanism known to generate active fragments of lower molecular mass. Endogenous IP(3)-3KB has therefore not been formally identified in tissues. We have probed a series of murine tissues with an antibody directed against the C-terminus of IP(3)-3KB and used IP(3)-3KB deficient mouse tissues as negative controls. IP(3)-3KB was shown to be particularly well expressed in brain, lung, and thymus with molecular masses of 110-120kDa. The identification of the native IP(3)-3KB by Western blotting for the first time will facilitate further studies of regulation of its activity by specific proteases and/or phosphorylation. 相似文献