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951.
952.
Elyse Y. Bissonnette PhD A.Dean Befus PhD 《The Journal of allergy and clinical immunology》1997,100(6):825-831
β2-Agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D2 from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-α (TNF-α), there is no information about their regulation by β2-agonists. Thus given the importance of TNF-α in inflammation and the widespread use of β2-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) β2-agonists on the secretion of TNF-α from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-α (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-α–sensitive cell line, WEHI-164, with an IC50 of 71, 50, and 29 nmol/L, respectively. Specificity for β-adrenergic receptors was shown with propranolol. The inhibitory effect of β2-agonists was observed after only 20 minutes of treatment but was lost by 24 hours after removal of salbutamol and isoproterenol (7% and 11% inhibition remaining, respectively). In contrast, the inhibition of TNF-α release was increased 1 hour after removal of salmeterol and remained significant 24 hours later. Furthermore, β2-agonists did not show tachyphylaxis for the inhibition of TNF-α release. Thus selective β2-agonists demonstrate anti-inflammatory activity by inhibiting the release of TNF-α from mast cells stimulated through their IgE receptor or by a tumor target cell. This inhibitory effect of β-agonists may be important in their mode of action in the treatment of allergic diseases. (J Allergy Clin Immunol 1997;100:825-31.) 相似文献
953.
954.
Cleide G. da Silva Ana Rúbia F. Bueno Patrícia F. Schuck Guilhian Leipnitz Csar A. J. Ribeiro Clvis M. D. Wannmacher Angela T. S. Wyse Moacir Wajner 《International journal of developmental neuroscience》2003,21(4):217-224
L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria. 相似文献
955.
GABAA receptor (GABAR) isoforms in the central nervous system are composed of combinations of α(1–6), β(1–4), γ(1–4), δ(1) and (1) subunit subtypes arranged in a pentamer. Many regions of the brain express high levels of mRNA encoding several different subunits and even multiple subunit subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and identity of individual subunit subtypes that are coassembled remain uncertain. To examine the role of β subunit subtypes in the functional properties of GABARS and to determine whether multiple β subtypes can be coassembled in functional GABARs, plasmids containing cDNAs encoding rat β1 and/or β3, α5 and γ2L subtypes were cotransfected into L929 fibroblasts. The properties of the expressed receptor populations were determined using whole-cell and single-channel recording techniques. The α5β1γ2L isoform was less sensitive to GABA than the α5β3γ2L isoform. α5β1γ2L isoform currents were also insensitive to the allosteric modulator loreclezole, while α5β3γ2L isoform currents were strongly potentiated by loreclezole. Fibroblasts transfected with plasmids containing cDNAs for both β1 and β3 subtypes along with α5 and γ2L subtypes produced a receptor population with an intermediate sensitivity to GABA which was insensitive to loreclezole. These results suggest that functional GABARs can be formed that contain two different β subunit subtypes with properties different from receptors that contain only a single β subtype and that the β subunit subtypes influence the response of GABARs to GABA and to the allosteric modulator loreclezole. 相似文献
956.
用胆红素结石(ps)兔模型进行实验,设单纯胆道梗阻(BO)组、梗阻和大肠杆茵感染(BOI)组及空白对照组,观察肝组织及胆汁氧自由基(OFR)变化情况及对PS的影响。实验结果:肝组织部分OFR、前列腺素E_2(RGE_2)及PS的动态变化趋势相似,三者呈正相关;BOI组的上述指标均较BO组为高。提示OFR可能促使PGE_2合成,后者致糖蛋白分泌而参与PS的形成;大肠杆菌感染可能在梗阻的基础上增多OFR的生成而增加了Ps的形成。 相似文献
957.
It was recently shown that streptokinase may induce clot formation in vivo by immunoglobulin G mediated platelet stimulation. We evaluated the in vitro effect of streptokinase on platelet function in 103 subjects, of whom 52 were < or = 30 years and 51 were > or = 50 years old. Although streptokinase inhibited platelet aggregation in the majority of cases, in nine the threshold concentration of ADP required to induce irreversible aggregation decreased with streptokinase (1 million Units. l-1) by 30% or more. This observation was confirmed in five of the nine by repeated measurements indicating reproducible streptokinase-induced platelet stimulation. Among the five, two were < or = 30, and three were > or = 50 years old. In none of the five subjects did the radio allergo sorbent test detect type E immunoglobulins directed against streptokinase in the serum. In contrast, in four of the five subjects, streptokinase-induced platelet hyperaggregability was suppressed by addition of goat antibodies against human immunoglobulin G, or F(ab')2-fragments of such antibodies. Acetylsalicylic acid did not prevent streptokinase-induced platelet stimulation, but in three of five cases, led to an increase in the control threshold concentration for ADP, so that after the decrease induced by streptokinase the threshold concentration for ADP was in the same range as before acetylsalicylic acid and streptokinase administration. Thus, streptokinase led to an inhibition of platelet aggregation in the majority of subjects evaluated. In a minority of five out of 103, however, streptokinase reproducibly caused platelet stimulation, presumably mediated by immunoglobulin G.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
958.
本文描述了姜根茎腐烂的三种症状类型:青枯型、黄腐型及黄枯型;分别由青枯细菌、腐霉菌及青桔细菌和腐霉苗引起,鉴定出4种致病腐霉:P(?)(?)P.(?)P.(?)和P.(?).通过接种试验,证明腐霉对姜有较强的致病力;与青枯细菌共同为害,病将更严重,故姜的根茎腐烂不完全是细菌青枯病。 相似文献
959.
吸入麻醉药对人血浆和血小板血栓素B2生成与血小板聚集的影响 总被引:6,自引:0,他引:6
目的:探讨吸入麻醉剂氟烷、安氟醚和异氟醚对人血浆血栓素B2(TXB2),血小板TXB2生成与血小板聚集的影响。方法:血浆TXB2和血小板TXB2的生成量用放免分析法测量,血小板聚集率用比浊法测量。结果:吸入1MAC氟烷30分钟后,血浆TXB2浓度、二磷酸腺苷(ADP)和肾上腺素(E)诱导的血小板TXB2生成量与血小板聚集率显著下降,吸入1MAC安氟醚30分钟后,血浆TXB2浓度和血小板TXB2生成量与血小板聚集率亦显著下降,其降低的程度比氟烷轻。吸入1MAC异氟醚对上述指标无明显影响。血小板TXB2生成的减少与血小板聚集率的下降呈显著正相关。结论:氟烷显著抑制血小板聚集,安氟醚次之,异氟醚对血小板聚集无明显影响。其机制可能与氟烷和安氟醚通过抑制血小板上血栓素A2受体的亲和力,降低ADP和E诱导的血小板TXB2的生成有关。 相似文献
960.
Facial nerve reconstruction in neurofibromatosis 2 总被引:1,自引:0,他引:1
Summary Between 1979 and 1989, 13 patients with neurofibromatosis 2 underwent reconstructions of the facial nerve after removal of bilateral acoustic or facial neurinomas. Seven patients received hypoglossal-facial nerve anastomosis, and five reveived sural nerve grafting in the cerebellopontine angle. End-to-end anastomosis and intracranial-intratemporal sural grafting were performed for one patient each, respectively. Re-innervation was seen in all cases. The results were good in 11 cases. Two patients presented with poor results due to development of neurinomas close to the site of the nerve reconstruction. The importance of reconstructive surgery in patients with neurofibromatosis is stressed. The problems regarding failure of re-innervation in some cases and difficulties in their management are discussed. 相似文献