全文获取类型
收费全文 | 201929篇 |
免费 | 16891篇 |
国内免费 | 7404篇 |
专业分类
耳鼻咽喉 | 1631篇 |
儿科学 | 2716篇 |
妇产科学 | 2283篇 |
基础医学 | 31979篇 |
口腔科学 | 3566篇 |
临床医学 | 14889篇 |
内科学 | 35453篇 |
皮肤病学 | 2833篇 |
神经病学 | 15009篇 |
特种医学 | 4308篇 |
外国民族医学 | 57篇 |
外科学 | 13435篇 |
综合类 | 27625篇 |
现状与发展 | 19篇 |
一般理论 | 6篇 |
预防医学 | 9477篇 |
眼科学 | 2072篇 |
药学 | 32494篇 |
43篇 | |
中国医学 | 8412篇 |
肿瘤学 | 17917篇 |
出版年
2024年 | 407篇 |
2023年 | 3567篇 |
2022年 | 7177篇 |
2021年 | 10142篇 |
2020年 | 7697篇 |
2019年 | 6527篇 |
2018年 | 6279篇 |
2017年 | 6370篇 |
2016年 | 6515篇 |
2015年 | 7644篇 |
2014年 | 11884篇 |
2013年 | 13269篇 |
2012年 | 11738篇 |
2011年 | 13550篇 |
2010年 | 11143篇 |
2009年 | 11419篇 |
2008年 | 11082篇 |
2007年 | 10191篇 |
2006年 | 9097篇 |
2005年 | 8036篇 |
2004年 | 6707篇 |
2003年 | 5977篇 |
2002年 | 4696篇 |
2001年 | 3887篇 |
2000年 | 3294篇 |
1999年 | 2948篇 |
1998年 | 2762篇 |
1997年 | 2558篇 |
1996年 | 2302篇 |
1995年 | 2054篇 |
1994年 | 1832篇 |
1993年 | 1581篇 |
1992年 | 1304篇 |
1991年 | 1244篇 |
1990年 | 1011篇 |
1989年 | 844篇 |
1988年 | 800篇 |
1987年 | 670篇 |
1986年 | 602篇 |
1985年 | 949篇 |
1984年 | 901篇 |
1983年 | 630篇 |
1982年 | 640篇 |
1981年 | 511篇 |
1980年 | 431篇 |
1979年 | 353篇 |
1978年 | 230篇 |
1977年 | 193篇 |
1976年 | 183篇 |
1975年 | 123篇 |
排序方式: 共有10000条查询结果,搜索用时 296 毫秒
991.
N. Limberger E. A. Singer K. Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(1):62-67
Summary Experiments were carried out in rabbit cerebrocortical slices in order to find out whether the attenuation by presynaptic 2-autoreceptors of effects mediated by presynaptic opioid - and adenosine A1-receptors requires activation of the 2-receptors. The slices were preincubated with 3H-noradrenaline and then superfused with medium containing desipramine 1 mol/l. They were stimulated electrically either with single pulses or with trains of 32 pulses at 1 Hz.The overflow of tritium elicited by a single pulse amounted to 0.21% of the tritium content of the tissue. It was Ca2+-dependent and tetrodotoxin-sensitive and not changed by rauwolscine 1 mol/l or yohimbine 0.3 mol/l. Ethylketocyclazocine (EK; 0.1–10 nmol/l) and R-(–)-N6-phenylisopropyladenosine (PIA; 1–1,000 nmol/1) potently inhibited the overflow evoked by a single pulse, and their effects were not changed by yohimbine. — The overflow of tritium elicited by trains of 32 pulses at 1 Hz amounted to 0.92% of the tritium content of the tissue and was increased approximately fourfold by yohimbine 0.3 mol/l. EK and PIA were less potent inhibitors than in the one pulse experiments. Yohimbine greatly enhanced the effects of EK and PIA. The enhancement was even more pronounced when the Ca2+ concentration in the medium was reduced in order to obtain a control tritium overflow similar to that evoked by 32 pulses in the absence of yohimbine.The results demonstrate that there is no 2-adrenergic autoinhibition when noradrenaline release is elicited by a single pulse. Under these conditions, the non-activated presynaptic 2-adrenoceptor does not interfere with presynaptic opioid - and adenosine A1-receptor mechanisms. It is only when the autoreceptor is activated by released noradrenaline that it attenuates neighbouring presynaptic receptor mechanisms, and this attenuation is removed by 2-adrenoceptor antagonists.Send offprint requests to N. Limberger at the above address 相似文献
992.
Katsuo Kamata Akemi Sakamoto Yutaka Kasuya 《Naunyn-Schmiedeberg's archives of pharmacology》1988,338(4):401-406
Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10–6 M serotonin, and the IC50 value for VIP was 2.4 × 10–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC50 value was 2.8 × 10–9 M in the presence of 10–6 M atropine and 10–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K+-channels.Send offprint requests to K. Kamata at the above address 相似文献
993.
Summary The handling of five amines by the extraneuronal deaminating system was studied in perfused hearts of rats (pretreated with reserpine; COMT and neuronal uptake inhibited). Hearts were perfused with 50 nmol/l 3H-noradrenaline for 30 min, in the presence of increasing concentrations of unlabelled (–)-adrenaline, (–)-noradrenaline, dopamine, tyramine and 5-HT. IC50's were determined as those concentrations of unlabelled amines which halved the steady-state rate of deamination of 3H-noradrenaline. After correction for changes in the tissue/medium ratio for 3H-noradrenaline, half-saturating outside concentrations were obtained. They increased in the order (–)-adrenaline (15 mol/l) — tyramine — dopamine — noradrenaline —5-HT (53 mol/l). The V
max for extraneuronal deamination was determined for 3H-(–)-adrenaline, 3H-(–)-noradrenaline and 3H-dopamine, as well as (by HPLC and electrochemical detection) for tyramine and 5-HT. It was low for (–)-adrenaline, intermediate for (–)-noradrenaline, dopamine and 5-HT, high for tyramine. For the three catecholamines the half-saturating outside concentrations of the extraneuronal deaminating system clearly exceeded those for the extraneuronal O-methylating system of the same organ (see Grohmann and Trendelenburg 1985), although the two enzymes appear to co-exist in the same cells, so that the same transport system is involved.Abbreviations COMT
catechol-O-methyl transferase
- DOMA
dihydroxymandelic acid
- DOPEG
dihydroxyphenylglycol
- 5-HT
5-hydroxytryptamine
- MAO
monoamine oxidase
Supported by the Deutsche Forschungsgemeinschaft (SFB 176)
Send offprint requests to U. Trendelenburg 相似文献
994.
Miwa Baba Ryozo Oishi Kiyomi Saeki 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(4):423-428
Summary The effects of opioids on the permeability of the blood-brain barrier (BBB) were examined in mice with sodium fluorescein as an indicator of the permeability. The brain was perfused with saline 30 min after injection of sodium fluorescein (40 mg/kg, i. v.) and examined by fluorometry. Morphine hydrochloride (0.3–10 mg/kg, s. c.) markedly increased the brain level of sodium fluorescein dose-dependently without influencing the plasma level, when administered 20 min before sodium fluorescein injection. Intracerebroventricularly (i. c. v.) injected morphine hydrochloride (0.5 and 1.0 Erg) increased the brain sodium fluorescein level. Buprenorphine (0.1 and 0.5 mg/kg, s. c.) was also effective. However, pentazocine, ethylketazocine, U-50488H and SKF-10047 had no significant influence. The i.c.v. administration of [D-Ala2, McPhe4, Gly(ol)5]enkephalin (0.1 g) and [D-Ala2, D-Leu5]enkephalin (0.5 g) but not of [D-Thr2, Leu5]enkephalin-Thr increased the brain level of sodium fluorescein significantly. A small dose of naloxone (i. p.) significantly inhibited the effects of morphine, buprenorphine, [D-Ala2, McPhe4, Gly(ol)5]enkephalin and [D-Ala3, D-Leu5]enkephalin. ICI-174864 co-administered i. c. v. with [D-Ala2, D-Leu5]enkephalin was ineffective in antagonizing the effect of the latter. These findings suggest that the stimulation of µ opioid receptors results in an increase in BBB permeability to sodium fluorescein.
Send offprint requests to K. Saeki 相似文献
995.
G. Molderings J. Likungu H. R. Zerkowski M. Gothert 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(4):408-414
Summary Spirally cut strips of human saphenous veins preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and, unless stated otherwise, of cocaine or desipramine. Tritium overflow was stimulated electrically (2 Hz). Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential 2-adrenoceptor agonist procaterol concentration-dependently increased the electrically evoked tritium overflow. Prenalterol, a -adrenoceptor agonist with moderate preference for 1-adrenoceptors, was ineffective. The concentration-response curve of isoprenaline was shifted to the right by the nonselective -adrenoceptor antagonist propranolol and by the preferential 2-adrenoceptor antagonist ICI 118,551, but was not affected by the 1-selective antagonist atenolol. In experiments on strips preexposed to adrenaline 10 nmol/l (i. e. a concentration higher than that which normally occurs in vivo) for 32 min in the absence of cocaine or desipramine, the electrically evoked 3H overflow was not affected 12 and 44 min after withdrawal of adrenaline, irrespective of whether propranolol was absent or present in the superfusion fluid. — In veins incubated with 3H-adrenaline, a considerable amount of the radioactivity was accumulated. During subsequent superfusion with 3H-adrenaline-free solution, electrical stimulation induced tritium overflow in a tetrodotoxin-sensitive manner. Propranolol failed to modify the evoked tritium overflow. — It is concluded that the sympathetic nerve fibres of the human saphenous vein are endowed with facilitatory presynaptic 2-adrenoceptors. These receptors do not seem to play a substantial role in a local adrenaline (previously taken up)-mediated positive feedback loop regulating noradrenergic transmission, at least under the present in vitro conditions.This study was supported by a grant of the Deutsche Forschungsgemeinschaft
Send offprint requests to M. Göthert 相似文献
996.
Martin J. Lohse Bernice Elger Jutta Lindenborn-Fotinos Karl-Norbert Klotz Ulrich Schwabe 《Naunyn-Schmiedeberg's archives of pharmacology》1988,337(1):64-68
Summary Human platelet membranes were solubilized with the zwitterionic detergent CHAPS (3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate) and the solubilized extract subjected to gel filtration. Binding of the adenosine receptor agonist [3H]NECA (5-N-ethylcarboxamidoadeno-sine) was measured to the eluted fractions. Two [3H]NECA binding peaks were eluted, the first of them with the void volume. This first peak represented between 10% and 25% of the [3H]NECA binding activity eluted from the column. It bound [3H]NECA in a reversible, saturable and GTP-dependent manner with an affinity of 46 nmol/1 and a binding capacity of 510 fmol/mg protein. Various adenosine receptor ligands competed for the binding of [3H]NECA to the first peak with a pharmacological profile characteristic for the A2 adenosine receptor as determined from adenylate cyclase experiments. In contrast, most adenosine receptor ligands did not compete for [3H]NECA binding to the second, major peak. These results suggest that a solubilized A2 receptor-GS protein complex of human platelets can be separated from other [3H]NECA binding sites by gel filtration. This allows reliable radioligand binding studies of the A2 adenosine receptor of human platelets.Abbreviations CHAPS
3-[3-(cholamidopropyl)dimethylammoniol-l-propanesulfonate
- CIA
2-chloroadenosine
- CPA
N6-cyclopentyladenosine
- DPX
1,3-diethyl-8-phenylxanthine
- NECA
5-N-ethylcarboxamidoadenosine
- PAA
2-phenylaminoadenosine
- PIA
N6-phenyhsopropyladenosine
- XAC
8-{4-[([{(2-aminoethyl)amino}carbonyl}methyl)oxy]phenyl]-1,3-dipropylxanthine
Send offprint requests to M. J. Lohse 相似文献
997.
The locomotor stimulant effects of sustained administration of a potent and selective dopamine (DA) D-2 receptor agonist, [+]-4-propyl-9-hydroxynaphthoxazine (PHNO), in rats were assessed 24 h a day during 12 h light-dark cycles. PHNO was administered continuously with subcutaneous implants of Alzet osmotic minipumps (5 g/h), for 12 h a day with modified osmotic minipumps (5 g/h), or by daily injections (15 g, SC). Tolerance was observed to occur only with 24 h continuous infusions and only during the light period. The other treatment regimens produced sensitization of the locomotor response. Daytime tolerance to continuous infusions of PHNO was reversed following reversal of the light-dark cycle. A normally arousing stimulus also reversed (temporarily) daytime tolerance. The present results indicate that the temporal pattern of administration of DA agonists, the phase of the circadian cycle and environmental stimuli associated with arousal are important determinants of the behavioral consequences of long-term treatment. 相似文献
998.
Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU. 相似文献
999.
Dermal toxicity of Fusarium toxins in combinations 总被引:3,自引:0,他引:3
T 2 toxin (T 2), diacetoxyscirpenol (DAS), fusarenon X (FX) and butenolide (Bd) at concentrations of 0.2, 0.3, 5 and 10 g/site, respectively, were applied individually and in combinations on shaved skin of guinea pigs. Erythema and induration were observed on skin patches treated with the toxins. Increase in the thickness of stratum malpighii was the major histological change observed. Mild to moderate degeneration of fibrocytes and cellular infiltration were found in the corium of skin treated with FX, Bd, DAS and T 2. The order of toxicity of individual toxins was T 2 > DAS > FX > Bd. Combinations of T 2 + FX and T 2 + Bd resulted in antagonism, while DAS + FX and DAS + Bd caused synergism. 相似文献
1000.
Dwyer VG Benson B Kwan KH Humphreys RC Ko WJ Lin NH Sammons DW 《Journal of pharmaceutical and biomedical analysis》1988,6(6-8):793-799
A reproducible and quantitative strategy for identifying tissue-specific proteins of the central nervous system is described. The methods include a simple extraction procedure, two-dimensional polyacrylamide gel electrophoresis (2-DGE), silver staining, and computerized analysis. Acetic acid protein extractions of brain regions from three groups of male Sprague—Dawley rats were compared by computer analysis using 2-DGE with GELCODE silver staining. Protein spot mapping and characterizations of molecular weight and pI were compiled for the pineal gland, retina, hypothalamus and cerebral cortex. Regionally specific protein spots were identified using the Visage System (BioImage) for data acquisition and a new set of algorithms (University of Arizona) for assigning isoelectric point (pI) and molecular weight determinations, spot matching and selection of unique spots. Seventeen newly identified acidic proteins are unique to the pineal gland. Some others are also common to the retina but not in other regions examined. Further study of these and other regionally specific proteins are of particular interest under conditions which alter biological or disease mechanisms. 相似文献