全文获取类型
收费全文 | 529篇 |
免费 | 25篇 |
国内免费 | 15篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 7篇 |
基础医学 | 38篇 |
口腔科学 | 9篇 |
临床医学 | 24篇 |
内科学 | 51篇 |
皮肤病学 | 2篇 |
神经病学 | 83篇 |
特种医学 | 2篇 |
外科学 | 17篇 |
综合类 | 48篇 |
预防医学 | 5篇 |
眼科学 | 9篇 |
药学 | 201篇 |
中国医学 | 7篇 |
肿瘤学 | 62篇 |
出版年
2023年 | 1篇 |
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 14篇 |
2018年 | 11篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 12篇 |
2014年 | 26篇 |
2013年 | 28篇 |
2012年 | 12篇 |
2011年 | 47篇 |
2010年 | 34篇 |
2009年 | 24篇 |
2008年 | 33篇 |
2007年 | 26篇 |
2006年 | 32篇 |
2005年 | 31篇 |
2004年 | 30篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 18篇 |
2000年 | 11篇 |
1999年 | 14篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 8篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 10篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有569条查询结果,搜索用时 15 毫秒
1.
Magnocellular neurons in rat hypothalamic slices are known to exhibit dye coupling: the transfer of the fluorescent dye, Lucifer Yellow, from an intracellularly-injected neuron to one or more nearby neurons. The question of the hormonal identity of coupled cells and the possibility of dye coupling as an artefact led us to determine the immunoreactivity of dye-coupled magnocellular neurons in the paraventricular nucleus of the rat hypothalamus using antisera to oxytocin- and vasopressin-associated neurophysins. In 23 pairs, one triplet, and one quadruplet, immunoreactivity to one or the other antiserum was always exclusive, and dye coupling was always homotypic, that is, coupled neurons in each instance were reactive to the same antiserum. The quadruplet, triplet and 17 pairs were immunoreactive to vasopressin-associated neurophysin, and oxytoxin-associated neurophysin immunoreactivity was observed in the remaining pairs. Immunoreactivity to each antiserum was found for somasomatic and non somasomatic modes of coupling and for coupled neurons in the three magnocellular areas of the nucleus. A relationship between mode of coupling and hormone content was not detected. The data support the hypothesis that coupling is a real, functionally significant mechanism for coordinating neuronal activity in this nucleus, particularly under conditions of high hormone demand. They do not support the idea that coupling is artefact. The possibility of a relationship between hormone content and mode of coupling, and the projection pathway(s) of the coupled neurons of each type require further study. 相似文献
2.
We evaluated the inhibitory effect of DS-4574, a peptidoleukotriene antagonist with mast cell stabilizing action, on rat gastric mucosal lesions induced by compound 48/80 (C48/80: a mast cell degranulator), in comparison with those of disodium cromoglycate (DSCG: a mast cell stabilizer), LY171883 (a peptidoleukotriene antagonist) and cimetidine (a histamine H2 receptor antagonist). Subcutaneous administration of C48/80 (1 mg/kg) once daily for four consecutive days produced extensive gastric lesions in the fundic mucosa. DS-4574 (20, 50 and 100 mg/kg/day, oral) and DSCG (200 mg/kg/day, intraperitoneal) treatment markedly inhibited formation of these mucosal lesions, but LY171883 (100 and 200 mg/kg/day, oral) and cimetidine (400 mg/kg/day, oral) treatment did not. Moreover, DS-4574 and DSCG significantly suppressed both hyperhistaminemia and histamine release from rat peritoneal mast cells induced by C48/80. These results indicate that the inhibitory effect of DS-4574 on gastric lesions induced by C48/80 may be related to its mast cell stabilizing action, but to neither its antisecretory nor its peptidoleukotriene antagonistic activity. 相似文献
3.
M. M. Foreman J. L. Hall 《Journal of neural transmission (Vienna, Austria : 1996)》1987,68(3-4):153-170
Summary The effects of selective D2-dopaminergic receptor stimulation with LY163502 on male rat copulatory behavior were evaluated. LY163502 (25 ng/kg to 25g/kg s. c.) produced increases in the percentage of sexually inactive rats displaying mounting behavior and ejaculating during the test period. Within this same dose range, LY163502 administration induced an increase in the percentage of non-ejaculator rats that were capable of ejaculation. These findings are viewed as evidence that LY163502 can initiate sexual behavior and lower the threshold for ejaculation. The effects of LY163502 were further evaluated in rats that were capable of ejaculation during the test period. LY163502 (25 ng/kg to 25g/kg s. c. or p. o.) induced significant reductions in ejaculatory latency. These effects were blocked by prior treatment with centrally active dopaminergic antagonists, RO 22-1319 and sulpiride, but not with a peripherally active antagonist, domperidone.LY163502 administration was also found to inhibit sexual behavior in low doses of 25 pg/kg –10 ng/kg s. c. and in a much larger dose of 25 mg/kg s. c. These inhibitory effects are viewed as behavioral manifestations of selective dopaminergic autoreceptor activation with low doses and as the disruption of sexual behavior by induction of intense stereotypic behavior with high doses. 相似文献
4.
Jerome H. Fleisch Lynn E. Rinkema Klaus D. Haisch Doris McCullough F. Patrick Carr Robert D. Dillard 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(1):70-77
Summary LY163443,1-[2-hydroxy-3-propyl-4-{[4-(1H-tetrazol-5-ylmethyl)-phenoxy]methyl}phenyl]ethanone, antagonized LTD4-induced contractions of guinea pig ileum, trachea, and lung parenchyma. Tracheal contractions to LTE4 were also inhibited by LY163443. The compound had minimal effect against ileal responses to LTC4 and parenchymal contractions to LTB4. Furthermore, LY163443.had little to no effect against contractions of isolated smooth muscles to histamine, bradykinin, PGF2, carbachol, serotonin or U46619. LY163443, given by oral administration to guinea pigs, blocked LTD4-induced increases in total pulmonary impedance (TPI). Similar responses elicited by histamine or U46619 were unaffected. Increases in TPI in response to i.v. administration of LTC4 were antagonized by LY163443 given by the same route. Ovalbumin challenge also increased TPI in guinea pigs previously sensitized against this antigen. In such animals, pretreated with pyrilamine, propranolol, and indomethacin, oral administration of LY163443 blocked the increase in TPI caused by ovalbumin. Additionally, LTD4 given intradermally to guinea pigs caused a vascular leakage which was suppressed by prior oral administration of LY163443. Finally, LY163443 relaxed isolated guinea pig trachea previously contracted with LTD4, histamine, or carbachol. Relaxation of tissues contracted by these latter two agonists suggested some inherent airway smooth muscle relaxant properties of the molecule. This was further demonstrated by showing some bronchodilator activity in an in vivo setting. Thus, this pharmacologic profile indicates that LY163443, or a member of the same chemical family, warrants consideration as a possible therapeutic agent in the treatment of asthma and in diseases characterized by an overproduction of LTD4 and LTE4.Presented in part at the meeting of The Federation of American Societies for Experimental Biology, April 1985, Anaheim, California. 相似文献
5.
NMDA receptor antagonism, but not AMPA receptor antagonism attenuates induced ischaemic tolerance in the gerbil hippocampus 总被引:5,自引:0,他引:5
Ann Bond David Lodge Caroline A. Hicks Mark A. Ward Michael J. O'Neill 《European journal of pharmacology》1999,380(2-3):91-99
Recent studies have shown that a brief ‘pre-conditioning' ischaemic insult reduces the hippocampal cell death caused by a subsequent more severe test insult. In the present studies, we have examined the effects of the non-competitive NMDA receptor antagonist ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine, MK-801) a competitive NMDA receptor antagonist, LY202157, AMPA receptor antagonist ((3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)]decahydroisoquinoline-3-carboxylic acid, LY293558), a non-competitive AMPA receptor antagonist ((−)-1-(4-amino-phenyl)-4-methyl-7,8-methylenedioxy-4,5-dihydro-3-acetyl-2,3-benzodiazepine, LY300164), and a mixed NMDA/AMPA receptor antagonist, LY246492, in a gerbil model of ischaemic tolerance. Ischaemic tolerance was induced by subjecting gerbils to a 2-min ‘pre-conditioning' ischaemia (bilateral carotid occlusion) 2 days prior to a 3-min test ischaemia. The effects of MK-801 (2 mg/kg i.p.), LY293558 (20 mg/kg i.p., followed by 4×10 mg/kg at 3 h intervals), LY300164 (4×10 mg/kg i.p. at 1 h intervals), LY246492 (40 mg/kg i.p., followed by 4×20 mg/kg i.p. at 3 h intervals) and LY202157 (30 mg/kg i.p., followed by 4×15 mg/kg i.p. at 2 h intervals) were then examined in this model. Initial dosing commenced 30 min prior to the 2-min ‘pre-conditioning' ischaemia. Results indicated that a 2-min ‘pre-conditioning' ischaemia produced ischaemic tolerance in all cases. The non-competitive NMDA receptor antagonist, MK-801, produced a significant (P<0.01) reduction in the induced tolerance, while the competitive NMDA receptor antagonist, LY202157, also attenuated (P<0.05) the induction of tolerance. In contrast, two AMPA receptor antagonists (LY293558 and LY300164) and a mixed NMDA/AMPA receptor antagonist (LY246492) had no effect on the induction of tolerance. These results suggest that NMDA receptor activation, but not AMPA receptor activation is involved in the phenomenon of ischaemic tolerance. 相似文献
6.
Kłodzińska A Chojnacka-Wójcik E Pałucha A Brański P Popik P Pilc A 《Neuropharmacology》1999,38(12):133-1839
Despite there being a lot of biochemical data about metabotropic glutamate (mGlu) receptors, our knowledge of the behavioural effects of mGlu receptor agonists/antagonists is still inadequate. LY 354740 is a systemically active agonist of group II mGlu receptors. After peripheral administration, LY 354740 produced anxiolytic-like effects in the conflict drinking test in rats and a four-plate test in mice. It was also found that LY 354740 decreased spontaneous locomotor activity in mice, but did not disturb motor coordination. In behavioural models of depression including the despair test and a tail suspension test, LY 354740 did not produce antidepressant-like effects. LY 354740 inhibited the naloxone-induced symptoms of morphine withdrawal in morphine-dependent mice. The above results indicate that agonists of group II mGlu receptors may play a role in the therapy of anxiety and/or drug-dependence states. The brain sites of action of LY 354740 need to be identified and the mechanism of both the above described effects remains to be elucidated. 相似文献
7.
Summary When islets were cultured with interleukin-1 (1 or 100 pmol/l) for 12 h in arginine-containing medium, cyclic GMP levels were increased 1.6- and 4.5-fold respectively. The arginine analogue, N--nitro-l-arginine methyl ester, which blocks nitric oxide formation and partially reverses inhibition of insulin secretion by 100 pmol/l interleukin-1, largely, but not completely, blocked generation of cyclic GMP. Treatment of islets with 100 pmol/l interleukin-1 for 12 h significantly decreased islet cyclic AMP generation in the absence of isobutylmethylxanthine (from 13.1±0.7 to 9.3±0.8 fmol/g islet protein), this fall was arginine-dependent and may have resulted from an effect on a cyclic AMP phosphodiesterase, since it was masked if isobutylmethylxanthine was present. Isobutylmethylxanthine (0.4 mmol/l) reduced the inhibitory potency of interleukin-1 in 15 h slightly but significantly from 80.5 to 59.0%. The morpholinosydnonimine SIN-1, which is a nitric oxide donor, inhibited insulin secretion, raised islet cyclic GMP and lowered cyclic AMP; its effects were similar to those of interleukin-1. However, 6-anilinoquinoline-5,8-quinone, [LY83583 (1–10 mol/l)], inhibited insulin secretion, and significantly decreased cyclic GMP while 8-bromocyclic GMP stimulated insulin secretion. Both low- and high-dose interleukin-1 treatment give a large arginine-dependent and a small, yet significant, arginine-independent increase in cyclic GMP. The inhibitory effect of SIN-1 or interleukin-1 on insulin secretion seems to depend to a small extent on decreased islet cyclic AMP, though sustained increases in nitric oxide or depleted islet GTP may directly affect the secretory process. 相似文献
8.
Hiroshi Masuno Jun Iwanami Teruki Kidani Kenshi Sakayama Katsuhisa Honda 《Toxicological sciences》2005,84(2):319-327
In order to identify whether bisphenol A (BPA) acts as an adipogenic agent, following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for six days with BPA alone. Treatment with BPA increased the triacylglycerol (TG) content of the cultures, increased the percentage of Oil Red O-staining cells in the cultures, and increased the levels of lipoprotein lipase (LPL) and adipocyte-specific fatty acid binding protein (aP2) mRNAs. These findings indicate that BPA was able to accelerate terminal differentiation of 3T3-L1 cells into adipocytes. LY294002, a chemical inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), blocked completely the increasing effect of BPA on TG accumulation and expression of LPL and aP2 mRNAs. Western blot analysis revealed that BPA increased the level of phosphorylated Akt kinase. Based on these findings, we concluded that BPA acted through the PI 3-kinase and Akt kinase pathway, resulting in increased TG accumulation and expression of adipocyte genes. The structure-activity relationship for BPA-related chemicals was examined. Eight derivatives of BPA (three diphenylalkanes with different substituents at the central carbon atom, three diphenylalkanes with ester bonds on hydroxyl groups in the phenolic rings, one bisphenol consisting of a sulphur atom at the central position, one chemical with cyanic groups, instead of hydroxyl groups, in the phenolic rings) accelerated terminal adipocyte differentiation and their potencies to increase TG accumulation were 73-97% of that of BPA. Two diphenylalkanes with ether bonds on hydroxyl groups and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) did not have the ability to accelerate terminal adipocyte differentiation. 相似文献
9.
The neurotoxic profile of (2S,4R, 6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434), a low-affinity kainate receptor subtype 5 (GluR5) agonist at recombinant human glutamate receptors, was evaluated to investigate the involvement of GluR5 in excitotoxic neuronal death. Murine cortical neurons were exposed to treatments for 24 h and assessed by a cell viability assay and phase-contrast microscopy. LY339434 (1-1000 microM) caused a concentration-dependent decrease in cell viability (EC(50)=11.4+/-1.2 microM) that was only attenuated by (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801, 10 microM), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) or 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466, 20 microM). Labeling with nucleic acid binding dyes revealed that LY339434 induced few apoptotic-like characteristics. These findings indicate that in cultured murine cortical neurons, LY339434 acts predominantly through N-methyl-D-aspartate (NMDA) receptors rather than GluR5 to effect neuronal death that is rapid and involves predominantly necrosis rather than morphological apoptosis. 相似文献
10.
Curcumin (diferuloylmethane) is a phenolic compound present in turmeric and is ingested daily in many parts of the world. Curcumin has been reported to cause inhibition on proliferation and induction of apoptosis in many human cancer cell lines, including non‐small cell lung cancer cells (NSCLC). However, the clinical application of curcumin is restricted by its low bioavailability. In this report, it was observed that combined treatment of a low dosage of curcumin (5–10 µ m ) with a low concentration (0.1–2.5 µ m ) of small molecule inhibitors, including AG1478, AG1024, PD173074, LY294002 and caffeic acid phenethyl ester (CAPE) increased the growth inhibition in two human NSCLC cell lines: A549 and H1299 cells. The observation suggested that combined treatment of a low dosage of curcumin with inhibitors against epidermal growth factor receptor (EGFR), insulin‐like growth factor 1 (IGF‐1R), fibroblast growth factors receptor (FGFR), phosphatidylinositol 3‐kinases (PI3K) or NF‐κB signaling pathway may be a potential adjuvant therapy beneficial to NSCLC patients. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献