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21.
Excitatory amino acids may cause neuronal damage and death in cerebral hypoxia and ischemia, through the activation of different subtypes of glutamate receptors, in particular of the
(NMDA) receptor. In the present work, the effect of hypoxia on the component of the field excitatory postsynaptic potential (fepsp) mediated by the NMDA receptor was studied in the hippocampal CA1 area of the rat. A period of 15 min of hypoxia induced virtual abolition of the NMDA receptor-mediated fepsp and a 94.8 ± 0.7% maximal decrease in the fepsp. A period of 3 min of hypoxia induced a 89.3 ± 12.3% maximal decrease in the NMDA receptor-mediated component of the fepsp and only a 50.8 ± 11.5% maximal decrease in the fepsp. Both periods of hypoxia thus induced a more pronounced depression of the NMDA receptor-mediated component of the fepsp than of the fepsp. We found that 48.5 ± 9.1% decrease (about half of the total decrease) in the NMDA receptor-mediated fepsp, and 51.6 ± 19.6% decrease (approximately all decrease) in the fepsp induced by hypoxia (3 min) were reversed in the presence of the selective adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM), and thus likely to be mediated by endogenous adenosine, through the activation of adenosine A1 receptors. On the other hand, under the conditions we assumed to be normoxic in our slices, DPCPX (50 nM) induced a much larger increase in the amplitude of the NMDA receptor-mediated fepsp compared to the increase in the fepsp, which suggest that endogenous adenosine is inhibiting predominantly the NMDA receptor-mediated fepsp under these conditions. Hypoxia markedly decreases the NMDA receptor-mediated fepsp in the hippocampal CA1 area. The contribution of endogenous adenosine to the inhibition of the NMDA receptor-mediated fepsp may be fundamental for its neuroprotective effects. 相似文献
22.
低剂量电离辐射对小鼠免疫器官cAMP和儿茶酚胺含量的影响 总被引:2,自引:0,他引:2
本文报道,75mGy/(12.5mGy/min)单次全身X射线照射后9小时用SRBC免疫C57BL/6小鼠,在免疫后4天和7天脾脏、胸腺和下丘脑cAMP含量均降低;而在免疫后4天脾脏去甲肾上腺素、肾上腺素和酪氨酸含量均增高,免疫后7天肾上腺素含量仍持续增高;当连接γ射线65mGy(0.015mGy/min,6h/d)全身照射小鼠后即刻或29小时后免疫,脾脏和下丘脑cAMP含量也均降低。提示,低剂量 相似文献
23.
目的 探讨胞嘧啶脱氨酶(cytimidine deaminase,CD)基因修饰神经干细胞及其基因表达。方法 通过构建真核表达质粒pCMVCD,限制性内切酶消化鉴定后,采用Lipofectamine 2000脂质体介导法转染新生大鼠室管膜下区神经干细胞(Neural stem cells,NSCs),G418筛选阳性克隆,加入不同浓度的5-氟胞嘧啶(5-Flourocytosine,5-FC),MTT比色法测定NSCs的生存率。结果 本实验成功地培养并鉴定了神经干细胞,并将CD基因成功地转染了神经干细胞,G418阳性NSCs对低浓度5-FC高度敏感。结论 CD基因修饰神经干细胞的离体实验研究为干细胞治疗研究提供依据。 相似文献
24.
The Y-maze was used to examine the effects of purines acting at A1 and A2 adenosine receptors upon spontaneous alternation, a model of working memory, in mice. In support of previous work, scopolamine produced a loss of spontaneous alternation behaviour to the 0.5 chance level. The A1 receptor selective agonist N6-cyclopentyladenosine (CPA) did not change spontaneous alternation behaviour alone, but it prevented the decrease of spontaneous alternation scores produced by scopolamine. The A1 receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) blocked the effect of CPA in combination with scopolamine but had no effect alone. The A2 receptor selective agonist (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), and the A2 receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect of alternation behaviour alone and did not modify the effect of scopolamine. The results indicate the ability of A1 but not A2 receptor activation to modify working memory deficits induced by scopolamine, but suggest that endogenous adenosine does not normally participate in working memory processes. 相似文献
25.
Masahiro Fujita Kazuhiko Ito Hiroshi Kawamoto Saburo Kashii Mihoko Norioka Sumie Monden Minoru Okuma 《European journal of haematology》1993,50(4):200-205
Abstract: A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 μmol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 × 105and 1 × 106cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10. 相似文献
26.
A. J. Lawrence Elena Krstew Bevyn Jarrott 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):303-308
The present study has employed in vitro electrophysiology and radioligand binding assays to determine whether dopamine and
adenosine receptors interact with each other on rat vagal afferent neurons. Preincubation of the isolated rat nodose ganglion
with the adenosine A2a agonists CGS 21680 or DPMA (Both 1 μM) resulted in a functional antagonism of the ability of dopamine to depolarise the preparation.
Specifically, the concentration-response curve to dopamine was significantly shifted to the right in the presence of CGS 21680
and DPMA. On the other hand, adenosine itself, A1 and A3 receptor agonists and ATP were all incapable of modulating the electrophysiological response to dopamine. In contrast to
the nodose ganglion, CGS 21680 did not significantly affect the ability of the dopamine D2 ligands quinpirole or raclopride to displace [125I]NCQ298 binding to dopamine D2 receptors in membranes prepared from rat dorsal brain stem. These data indicate the presence of an interaction between high
affinity adenosine A2 receptors and dopamine D2 receptors on the soma of rat vagal afferent neurons, whereas the situation in the brain stem remains less clear.
Received: 17 September 1996 / Accepted: 20 October 1996 相似文献
27.
S. M. O. Hourani S. J. Bailey C. R. Johnson J. P. Tennant 《Naunyn-Schmiedeberg's archives of pharmacology》1998,358(4):464-473
The functional effects of adenosine 5’-triphosphate (ATP), uridine 5’-triphosphate (UTP), adenosine 5’-tetraphosphate (AP4) and the diadenosine polyphosphates P1,P3-diadenosine triphosphate (Ap3A), P1,P4-diadenosine tetraphosphate (Ap4A) and P1,P5-diadenosine pentaphosphate (Ap5A) were studied in two isolated smooth muscle preparations thought to contain P2Y (P2Y1) receptors, the guinea-pig taenia caeci (which relaxes to ATP) and the rat colon muscularis mucosae (which contracts to ATP).
In addition, the breakdown of these compounds by the rat colon muscularis mucosae was investigated by high pressure liquid
chromatography. In the guinea-pig taenia caeci all the purine nucleotides caused relaxation with a potency order of Ap3A=Ap4A> ATP>AP4=Ap5A, and these relaxations were antagonised by suramin with apparent pA2 values in the region of 5, consistent with activation of a P2Y1 receptor. In the rat colon muscularis mucosae the nucleotides caused contraction with a potency order of Ap3A = Ap4A>ATP=AP4 =Ap5A >UTP. However, while suramin (100 μM) inhibited responses to ATP and UTP at all concentrations of agonist, it only inhibited
contractions induced by the higher concentrations of AP4, Ap3A and Ap4A and had little effect on contractions induced by Ap5A. A higher concentration of suramin (1 mM) enhanced contractions induced by ATP but greatly inhibited those induced by UTP
and had no effect on responses to the other agonists. The A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM) had no effect on responses to ATP or UTP
but inhibited responses to Ap3A, Ap4A, Ap5A and AP4. A combination of suramin (1 mM) and DPCPX (10 nM) almost abolished responses to all the agonists. ATP and UTP were rapidly
degraded by the rat colon muscularis mucosae while AP4, Ap3A, Ap4A and Ap5A were degraded more slowly, and the major product detected after breakdown of the purine nucleotides was inosine rather than
adenosine. The breakdown of all the nucleotides was inhibited by suramin (1 mM), although this inhibition did not achieve
statistical significance in the case of ATP. These results show that while the diadenosine polyphosphates appear to act as
P2 agonists in the taenia caeci, in the rat colon muscularis mucosae their major action is via adenosine A1 receptors rather than via P2 receptors. In addition, although they are more stable than ATP or UTP, their action in this
tissue is clearly affected by their degradation which complicates the effects of suramin.
Received: 23 March 1998 / Accepted: 29 June 1998 相似文献
28.
P. Schubert T. Ogata S. Ferroni A. McRae Y. Nakamura K. Rudolphi 《Journal of molecular neuroscience : MN》1996,28(1-3):185-190
In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative
diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we
are particularly focusing on the endogenous modulation of the Ca2+ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline
(PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation
rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level
favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function.
On the other hand, a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties
of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine
effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by
modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which
a pathological activation of microglial cells and astrocytes is discussed to play a pathogenic role. 相似文献
29.
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
30.
The regional distribution of adenosine-regulating enzymes in the left and right ventricle walls of control and hypertrophic heart 总被引:3,自引:0,他引:3
V. De Tata S. Gini I. Simonetti V. Fierabracci Z. Gori P. L. Ipata Prof. E. Bergamini 《Basic research in cardiology》1989,84(6):597-605
Summary The transmural distribution of the adenosine-generating enzyme 5-nucleotidase (5N) and of the adenosine-degrading enzymes adenosine deaminase (ADA), AMP deaminase (AMP-D) and adenosine kinase (Ado-K) were determined across the walls of left and right ventricles of control and hypertrophic rat hearts.The enzyme distribution across the left ventricle wall (but not across the right wall) of normal hearts was not uniform: 5N activity shows its highest levels in the subepicardial and in the subendocardial regions, whereas all the other enzyme activities show their lowest levels. A similar pattern of transmural distribution was also detected in other mammalian species (ox and pig).In the experimental cardiac hypertrophy, caused by two different types of chronic cardiac overload, the levels and the profiles of transmural distribution of 5N and ADA enzyme activities may significantly change across the rat left ventricle wall. 相似文献