全文获取类型
收费全文 | 207篇 |
免费 | 4篇 |
出版年
2023年 | 1篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2016年 | 1篇 |
2015年 | 2篇 |
2014年 | 6篇 |
2013年 | 12篇 |
2012年 | 7篇 |
2011年 | 9篇 |
2010年 | 6篇 |
2009年 | 7篇 |
2008年 | 7篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2005年 | 10篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2002年 | 10篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 8篇 |
1994年 | 9篇 |
1993年 | 9篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1974年 | 1篇 |
排序方式: 共有211条查询结果,搜索用时 15 毫秒
1.
Local spinal cord vasomotor effects of 3 substance P (SP) antagonists were studied in the rat following intrathecal (IT) administration. Each SP antagonist (3.3 nmol) increased spinal cord vascular resistance and reduced blood flow. A LH-RH antagonist analog (10 nmol) of similar molecular weight and which also contained multiple D-Trp residues did not cause spinal cord vasoconstriction. The vasoconstrictor action of the SP antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP ([D-Arg]-SP) was unaffected by pretreatment with a stable SP receptor agonist (5 nmol IT). Given evidence for a cerebral vasodilator action of TRH agonists, the effects of TRH (IV) and a stable TRH analog (MK-771, IT) on [D-Arg]-SP-induced vasoconstriction were also assessed. Neither TRH nor MK-771 prevented the [D-Arg]-SP-induced vasoconstriction. However, TRH (IV) but not MK-771 (IT) partially opposed [D-Arg]-SP-induced reduction in thoracic spinal cord blood flow. Thus, SP antagonists cause spinal cord vasoconstriction by a non-SP receptor mediated phenomenon. In addition, the attenuation of SP-antagonist-induced neuropathological changes previously reported with IV. TRH administration is likely due to less severe consequences of vasoconstriction in the presence of a higher initial baseline blood flow rather than direct prevention of the vasoconstriction. 相似文献
2.
The indirect chiral separation of the four stereoisomers (1)-(4) of a novel carbonic anhydrase inhibitor with two chiral centers in the molecule is reported. The method is based on chemical derivatization of the secondary amino group of the inhibitor with chiral isocyanate, formation of diastereomeric urea derivatives, each with three chiral centers in the molecule, and their separation under nonchiral HPLC conditions. The attempts to separate racemic mixture (1) + (2) from its diastereomeric counterpart (3) + (4) under nonchiral conditions, and to separate enantiomers (1) and (2) directly on a chiral stationary phase (CSP) are also reported. The indirect method was utilized for the assessment of an in vivo inversion of configuration at either one or both chiral centers of the molecule of (1). Analyses of selected whole blood and urine samples from human subjects after multiple bilateral topical ocular dosing with (1) did not reveal the presence of any of the three possible stereoisomers (2)-(4) of (1) indicating that the inversion of configuration at neither one nor two chiral centers of (1) occurs in vivo. 相似文献
3.
大鼠杏仁核内注射八肽胆囊收缩素(CCK—8)拮抗吗啡镇痛的研究 总被引:2,自引:0,他引:2
大鼠双侧杏仁核内注射CCK-81ng(1μl),能明显降低皮下注射4mg/kg吗啡产生的镇痛作用,并在0.1-1ng范围内呈量效关系。分别向双侧仁核注射CCK-A受体拮抗剂Devazepide50ng能部分翻转,200ng则完全翻转CCK-8的抗吗啡镇痛作用,10ng无效;而CCK-B受体拮抗剂L-365,260在5-8ng时即可完全番转CCK-8的抗吗啡镇痛作用。杏仁核注射200ng的Devaz 相似文献
4.
Drugs of abuse, such as phencyclidine (PCP), methamphetamine (METH), and cocaine (COC) are known to affect several behaviors
in rats, such as motor activity, stereotypy, and circling. In this study, we evaluated whether these drugs produce circling
preferences in the presence or absence of unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the caudate nucleus. Adult
male CD rats were lesioned with 10 μg 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip), its congener, (+) MK-801 (0.15
mg/kg, ip), METH (2 mg/kg, ip), COC (60 mg/kg, ip), or apomorphine (0.2 mg/kg, ip). circling preference was recorded in control
and lesioned rats for 2 h before animals were sacrificed to determine monoamine levels by HPLC/EC. In control animals, administration
of these drugs produced 60–70% left circling. In, lesioned animals, these drugs produced 78–90% ipsilateral (toward the lesion)
circling, except apomorphine, which produced 60–80% contralateral (away from the lesion) circling. Dopamine (DA) and its metabolites
3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations significantly decreased ipsilaterally in
lesioned caudate nucleus (CN) and substantia nigra (SN). However, no significant changes were observed in nucleus accumbens
(NA) and olfactory tubercles (OT). These data demonstrate that drugs of abuse like PCP, its congener (+) MK-801, METH, and
COC produce a greater preference to turn toward the left than the right, a finding similar to that found in human psychosis.
Since 6-OHDA lesions enhanced the circling bias and depleted DA and its metabolites DOPAC and HVA, it also suggests that the
dopaminergic system may be involved in the circling behavior. 相似文献
5.
Summary In the present study the binding of [3H]MK-801 to glutamatergic receptors of the NMDA type was compared in spontaneously hypertensive (SHR) and normotensive (WKY) rats in various brain structures (including nucleus tractus solitarii) by quantitative receptor autoradiography. Additionally, blood pressure changes after treatment with the NMDA antagonist MK-801 were studied in both strains. There were no differences between SHR and WKY rats either in the level of [3H]MK-801 binding or in the hypertensive reaction to MK-801. 相似文献
6.
Neuronal and Glial Marker Proteins in the Evaluation of the Protective Action of MK 801 总被引:1,自引:0,他引:1
K. G. Haglid S. Wang A. Hamberger A. Lehmann C. J. Moller 《Journal of neurochemistry》1991,56(6):1957-1961
A quantitative dot immunobinding procedure was used to quantify glial [the S-100 protein and the glial fibrillary acidic (GFA) protein] and neuronal (the 68- and 200-kDa neurofilament polypeptides, neuron-specific enolase, and neuronal cell adhesion molecule) markers. A single intraperitoneal administration of 10 mg/kg of MK 801 blocked the increase of glial parameters and the decrease in content of neuronal marker proteins that occurred as the response to an N-methyl-D-aspartate (NMDA) lesion in the rat hippocampus. The degradation products of GFA protein and the 68-kDa neurofilament polypeptide that were induced by the NMDA lesion did not appear after MK 801 treatment. This study shows that brain-specific proteins are a set of precise tools for the evaluation of neuroprotective effects of antagonists to excitatory amino acids. 相似文献
7.
Margot H. M. Bakker Ruth M. McKernan Erik H. F. Wong Alan C. Foster 《Journal of neurochemistry》1991,57(1):39-45
The N-methyl-D-aspartate (NMDA) receptor is thought to contain several distinct binding sites that can regulate channel opening. In the present experiments, the effects of ligands for these sites have been examined on [3H]MK-801 binding to a soluble receptor preparation, which had been passed down a gel filtration column to reduce the levels of endogenous small-molecular-weight substances. Glycine site agonists, partial agonists, and antagonists gave effects similar to those observed in membranes [EC50 values (in microM): glycine, 0.31; D-serine, 0.20; D-cycloserine, 1.46; (+)-HA-966, 4.06; and 7-chlorokynurenic acid, 1.81]. Spermine and spermidine enhanced [3H]MK-801 binding to the soluble receptor preparation (EC50, 4.3 and 20.1 microM, respectively), whereas putrescine and cadaverine gave small degrees of inhibitions. When spermine and spermidine were tested under conditions where [3H]MK-801 binding approached equilibrium, their ability to enhance [3H]MK-801 binding was much reduced, a result suggesting that the polyamines increase the rate to equilibrium. Putrescine antagonised the effects of spermine. Ifenprodil reduced [3H]MK-801 binding under both equilibrium and nonequilibrium conditions, although the high-affinity component of inhibition described in membranes was not observed. Ifenprodil antagonised spermine effects in an apparently noncompetitive manner. Desipramine was able to give total inhibition of specific [3H]MK-801 binding under nonequilibrium conditions with an IC50 of 4 microM, and this value was unaltered when [3H]MK-801 binding was allowed to reach equilibrium. These results suggest that the sites mediating the effects of glycine and its analogues, polyamines and desipramine are integral components of the NMDA receptor protein. 相似文献
8.
Alessandro Zuddas Germano Oberto Francesca Vaglini Flavia Fascetti Francesco Fornai Giovanni U. Corsini 《Journal of neurochemistry》1992,59(2):733-739
In cynomologus monkeys, systemic administration of MK-801, a noncompetitive antagonist for the N-methyl-D-aspartate receptor, prevented the development of the parkinsonian syndrome induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MK-801 also attenuated dopamine depletion in the caudate and putamen and protected dopaminergic neurons in the substantia nigra from the degeneration induced by the neurotoxin. Nevertheless, 7 days after MPTP administration in the caudate and putamen of monkeys also receiving MK-801, the levels of toxic 1-methyl-4-phenylpyridinium were even higher than those measured in monkeys receiving MPTP alone. This indicates that the protective action of MK-801 is not related to MPTP metabolism and strongly suggests that, in primates, the excitatory amino acids could play a crucial role in the mechanism of the selective neuronal death induced by MPTP. 相似文献
9.
《Cell cycle (Georgetown, Tex.)》2013,12(21):4079-4092
Erlotinib was originally developed as an epidermal growth factor receptor (EGFR)-specific inhibitor for the treatment of solid malignancies, yet also exerts significant EGFR-independent antileukemic effects in vitro and in vivo. The molecular mechanisms underlying the clinical antileukemic activity of erlotinib as a standalone agent have not yet been precisely elucidated. Conversely, in preclinical settings, erlotinib has been shown to inhibit the constitutive activation of SRC kinases and mTOR, as well as to synergize with the DNA methyltransferase inhibitor azacytidine (a reference therapeutic for a subset of leukemia patients) by promoting its intracellular accumulation. Here, we show that both erlotinib and gefitinib (another EGFR inhibitor) inhibit transmembrane transporters of the ATP-binding cassette (ABC) family, including P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP), also in acute myeloid leukemia (AML) cells that do not overexpress these pumps. Thus, inhibition of drug efflux by erlotinib and gefitinib selectively exacerbated (in a synergistic or additive fashion) the cytotoxic response of KG-1 cells to chemotherapeutic agents that are normally extruded by ABC transporters (e.g., doxorubicin and etoposide). Erlotinib limited drug export via ABC transporters by multiple mechanisms, including the downregulation of surface-exposed pumps and the modulation of their ATPase activity. The effects of erlotinib on drug efflux and its chemosensitization profile persisted in patient-derived CD34+ cells, suggesting that erlotinib might be particularly efficient in antagonizing leukemic (stem cell) subpopulations, irrespective of whether they exhibit or not increased drug efflux via ABC transporters. 相似文献
10.
Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathway, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus. 相似文献