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991.
H. Gron R. Pike J. Potempa J. Travis I. B. Thøgersen J. J. Enghild S. V. Pizzo' 《Journal of periodontal research》1997,32(1):61-68
Porphyromonas gingivalis is closely associated with the development of some forms of periodontitis. The major cysteine proteinases released by this bacterium hydrolyze peptide bonds only after arginyl (gingipain R) or lysyl residues (gingipain K). No target protein inhibitors have been identified for either enzyme, leading us to investigate their inhibition by human plasma α2 -macroglobulin (α2 M). Both 50- and 95 kDa gingipain R were efficiently inhibited by α2 M, whereas the catalytic activity of gingipain K could not be eliminated. All 3 enzymes were, however, inhibited by a homologous macroglobulin from rat plasma, α1 -inhibitor-3 a-Macroglobulins must be cleaved in the so-called "bait region" in order to inhibit proteinases by a mechanism involving physical entrapment of the enzyme. A comparison of the aminio acid sequences of the 2 macroglobulins indicates that the lack of lysyl residues within the bait region of α2 M protects Lys-specific proteinases from being trapped. On this basis, other highly specific proteinases might also not be inhibited by α2 M, possibly explaining the inability of the inhibitor to control proteolytic activity in some bacterially induced inflammatory states, despite its abundance (2-5 mg/ml) in vascular fluids. 相似文献
992.
Attenuation of myocardial injury due to oxygen free radicals(OFR) by pretreatment with OFR or calcitonin gene-related peptide 总被引:3,自引:0,他引:3
目的:研究氧自由基(OFR)及降钙素基因相关肽(CGRP)预处置对OFR所致离体大鼠心脏损伤的拮抗作用.方法:Langendorf法灌流心脏,电解KH液产生OFR.结果:CGRP或OFR预处置减轻OFR所致心脏收缩功能下降,冠脉流量减少和肌酸激酶(CK)释放增加.蛋白激酶C(PKC)抑制剂H7可取消OFR预处置的心脏保护作用(对照组,OFR损伤组,OFR预处置组,H7加OFR预处置组及H7组的CK释放量分别是110±7,215±23,169±14,240±30,113±19U·L-1).结论:OFR或CGRP预处置对OFR所致心肌损伤具有拮抗作用,该作用与PKC激活有关. 相似文献
993.
Previous study has shown that α2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the
tissue location of α-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic α-adrenoceptors were
characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions
of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic α-adrenoceptors were identified
by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting
transmurally-induced contraction was: clonidine ≥ oxymetazoline ≥ UK 14,304 ≥ guanfacine > talipexole > phenylephrine > azepexole.
The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation.
Most of the α-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response
to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine,
idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pKB values best correlated with pKB or pKi values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the α2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine ≥
oxymetazoline > clonidine ≥ talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 μM. The EC50 value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular
muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of
carbachol-contracted tissues. It is concluded that the recently identified α2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also
demonstrated the presence of postsynaptic α1-adrenoceptors involved in mediating relaxation in both muscle layers.
Received: 4 November 1996 / Accepted: 10 April 1997 相似文献
994.
兴奋性氨基酸类神经毒剂与粉防己碱(tetrandrine,Tet)共同作用于原代培养胎鼠大脑皮层神经元24小时,发现107,106mol·L1Tet明显降低50μmol·L1谷氨酸(glutamate,Glu),300μmol·L1βNmethylaminoLalanine(BMAA,NMDA受体激动剂)和20μmol·L1βNoxalylaminoLalanine(BOAA,nonNMDA受体激动剂)导致的培养液乳酸脱氢酶(lactatedehydrogenase,LDH)活性的增高;细胞形态损害减轻,细胞数量增加。对20μmol·L1NMDA介导的神经元损伤改变无影响。提示Tet对某些Glu类神经毒剂引起的胎鼠大脑皮层神经元损伤有一定保护作用,其机制可能是抑制细胞膜上的Na+通道开放,阻止膜去极化而影响电压依赖性Ca2+通道启动。对NMDA受体可能亦有一定作用。 相似文献
995.
NOEL S. STURM ANN MARIE HUTZLER CLINTON S. DAVID BASSEM Y. AZIZEH DEV TRIVEDI VICTOR J. HRUBY 《Chemical biology & drug design》1997,49(4):293-299
We have designed and synthesized eight compounds 2-9 which incorporate neutral, hydrophobic amino acid residues in positions 9, 11 and 16 of the glucagon molecule: (2) [desHis1,Va19,11e11,16] glucagon amide, (3) [desHis1,Val9,11,16]glucagon amide, (4) [desHis1,Va19,Leu11,16]glucagon amide, (5) [desHis1,Nle9,11e11,16]glucagon amide, (6) [desHis1,Nle9,Val11,16]glucagon amide, (7) [desHis1,Nle9,Leu11,16]glucagon amide, (8) [desHis1,Val9,Leu11,16,Lys17,18,Glu21]glucagon amide and (9) [desHis1,Nle9,Leu11,16,Lys17,18,Glu21]glucagon amide. The effect of neutral, hydrophobic residues at positions 9, 11 and 16 led to good binding to the glucagon receptor. Compared to glucagon (IC50= 1.5 nM), analogues 2-9 were found to have IC50 values of 6.0, 6.0, 11.0, 9.0, 2.5, 2.8, 6.5 and 7.0 nM, respectively. When these compounds were tested for their ability to block adenylate cyclase (AC) activity, they were found to be antagonists having no stimulation of adenyl cyclase, with PA2, values of 6.15, 6.20, 6.30, 7.25, 6.10, 7.30, 6.25 and 7.25, respectively. © Munksgaard 1997. 相似文献
996.
The most commonly used photoaffinity labeling probes are compared, which are aryl azides, aryl diazirines, α-diazocarbonyls and benzophenone-derivatives. The compounds were used under identical conditions and crosslinking efficiency, influence of water, irradiation requirements, and by-products were investigated. Using the pentapeptide thymopentin (TP5) as a model system, we synthesized four analogues by solid-phase peptide synthesis and partially N-terminal modification to obtain [p-(3-trifluoromethyl)diazirinophenylalanine5] TP5, [p-benzoylphenylalanine5] TP5, 4-azidobenzoyl-TP5 and 2-diazo-3, 3, 3-trifluoropropionyl-TP5. The peptides were characterized by HPLC and ion-spray mass spectroscopy. Irradiation of the peptides with two different ultraviolet sources was carried out in water, n-propanol and water/n-propanol to imitate both hydrophobic and hydrophilic peptide/protein-interactions as well as the influence of the aqueous environment. Analysis of the products with HPLC, ion-spray MS, HPLC-MS and HPLC-CID-MS revealed that (Tmd)Phe is a highly potent carbene-precursor, which can be transformed easily into uniform crosslinking products by smooth photolysis. However, the electrophilic nature of the intermediate causes a high tendency to react with water molecules. The 4-azidobenzoyl group showed comparable crosslinking efficiency, but the probability to create non-uniform irradiation products (e.g. through rearrangement) is higher, whereas the reaction with water is less dominant. In contrast, Bpa was found to have an extremely low affinity to react with water, whereas prolonged UV irradiation is needed to get complete rearrangement into a variety of products. As the absorption band of α-diazocarbonyls at around 350 nm possesses a low extinction coefficient, 2-diazo-3, 3, 3-trifluoropropionyl-TP5 could not be activated at all with the optimized irradiation conditions that we have chosen for our comparative studies. © Munksgaard 1997. 相似文献
997.
7β-(6-取代-2-喹诺酮-3-乙酰氨基)头孢菌素的合成 总被引:1,自引:0,他引:1
以6-取代-2-喹诺酮-3-乙酸为侧链,用CDI法和潘化酯法与7-ADCA,7-ACA,7-ACT,和7-ACD缩合,合成了16个新的7β-(6-取代-2-喹诺酮-3-乙酰氨基)头孢菌素类化合物,通过溶媒转提,葡聚糖凝胶(Sephadex LH-20)柱层析及离心薄层层析分离精制,得到纯品。初步体外抑菌试验表明:新化合物对革兰氏阳性及某些阴性菌具有高度敏感性。大多数化合物对所试试验菌的抗菌活性与头孢唑啉和青霉素G钠相当,有些比它们还强。 相似文献
998.
Patrice Venault Georges Chapouthier Jacques Simiand Robert H. Dodd Jean Rossier 《Brain research bulletin》1987,19(3)
Benzodiazepines are known to induce a profound anterograde amnesia in man. In this report, it is shown that methyl β-carboline-3-carboxylate (β-CCM), an inverse agonist of the benzodiazepine receptor, has the opposite effect; it enhances performance in learning and memory tasks. Three different learning models were used: habituation to a new environment and passive avoidance in mice and imprinting in chicks. The opposite effects of both β-CCM and the benzodiazepine diazepam were blocked by administration of the benzodiazepine receptor antagonist Ro 15-1788, provicling evidence that the benzodiazepine receptor is involved in these effects. 相似文献
999.
Kim Hahn Le Quan Sang Jean-Luc Elghozi Philippe Meyer Marie-Aude Devynck 《Clinical and experimental pharmacology & physiology》1987,14(3):187-189
1. Plasma renin activity (PRA) and platelet cytosolic free calcium concentration ([Ca2+]i) were simultaneously determined in 18 untreated essential hypertensive subjects and 17 normotensive controls. A significant positive correlation was found between [Ca2+]i and PRA (slope = 42 nmol/l/ng/ml/h) in these 35 subjects. 2. Two determinations more than one week apart in nine subjects confirmed the parallel fluctuations of [Ca2+]i and PRA. A strict sodium restriction produced a progressive PRA elevation associated with a parallel rise in [Ca2+]i in one subject. 3. These results are consistent with the hypothesis that angiotensin II causes a concentration-dependent calcium mobilization. 相似文献
1000.
Hikaru Tanaka Naofumi Uesato Koki Shigenobu 《Naunyn-Schmiedeberg's archives of pharmacology》1995,351(4):391-397
Chronotropic and inotropic effects of histamine were examined in isolated atrial and ventricular preparations from embryonic and hatched chicken hearts. Histamine produced positive chronotropic and inotropic responses both in embryonic and hatched hearts. The responses to histamine in middle embryonic myocardia, which were observed in the micromolar range, were antagonized by H2 antagonists but not by H1, H3 antagonists and propranolol. Isobutylmethylxantine, an inhibitor of phosphodiesterase, produced a leftward shift of the concentration-response curve for the chronotropic effect of histamine in the embryo. The responses to histamine in myocardia from hatched chicks, which were observed in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations were greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing chicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H2 receptors in the embryonic heart and release of norepinephrine from sympathetic nerve terminals in hatched hearts. 相似文献