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11.
Stereochemistry of Substituted Glutaric Acids, II: Syntheses of Substituted 3-(4-Fluorophenyl)-glutaric Acids The stereoselective syntheses of (±)erythro- and (±) threo-3-(4-fluorophenyl)-2-methyl-glutaric acids (9), (10) by Michael addition of dimethyl malonate (2) to methyl E-2-methyl-4′-fluorocinnamate (1) via the subst. trimethylbutanetricarboxylates 3,4 and the subst. butanetricarboxylic acids 7,8 are described. 3 and 4 have been alkylated with methyl bromoacetate to the subst. tetramethylpentanetetracarboxylates 5 and 6 . Attempts towards saponification of 5 and 6 are reported. 相似文献
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The role of alpha-haemolysin (AH) in the resistance of Escherichia coli strains, isolated from patients with extra-intestinal diseases or diarrhoea, to the bactericidal activity of human serum and intracellular killing in polymorphonuclear leucocytes (PMNL) was investigated in vitro. Sets of alpha-haemolytic and non-haemolytic E. coli strains and sets of isogenic E. coli strains, which included wild-type alpha-haemolytic strains and derived strains with a reduced production of AH, were used. Compared with non-haemolytic strains, alpha-haemolytic strains were significantly more resistant to the bactericidal activity of 10% and 100% human serum and to intracellular killing in PMNL. Higher resistance to serum killing and to intracellular killing in PMNL was also found in wild-type alpha-haemolytic E. coli than in isogenic bacteria with reduced production of AH. These results provide evidence that production of AH in E. coli strains counteracts both the bactericidal activity of serum and intracellular killing in PMNL. 相似文献
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Thomas Müller Christoph Erdmann Siegfried Muhlack Dirk Bremen Horst Przuntek Dirk Woitalla 《Journal of clinical neuroscience》2007,14(5):424-428
BACKGROUND: A possible strategy to prolong plasma metabolism of Levodopa/Carbidopa (LD/CD) is Entacapone addition (EN), which improves impaired motor behaviour in patients with Parkinson's disease (PD). AIMS OF THE STUDY: Objectives were to evaluate the clinical response to an increased dopaminergic substitution with EN by clinical rating and assessment of complex motions and to investigate the change of movement in PD patients during repeat drug administration during an eight hour interval. METHODS: We used peg insertion with a computer based device and clinical rating for assessment of motor function in 20 treated PD patients. They received LD/CD and then the same LD/CD dosage plus EN in a standardised, open label fashion. RESULTS: Motor scores and performance of the instrumental task were significantly better and the fluctuation of movement was less intense during the LD/CD/EN condition according to the motor test outcomes. CONCLUSION: EN supplementation improves motor symptoms and provides a more continuous movement behaviour in PD patients. 相似文献
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Siegfried Scherer Gerhard Herrmann Joseph Hirschberg Peter Böger 《Current genetics》1991,19(6):503-507
Summary When only plastidic features are considered, it is difficult to distinguish between monophyletic and polyphyletic xenogenous origins of plastids. We suggest that a direct comparison of nuclear and plastidic sequence-similarity pattern will help to solve this problem. The D1 amino acid sequence of six major groups of photosynthetic eukaryotes and of the two groups of photosynthetic prokaryotes are now available, including the psbA-gene product from Bumilleriopsis filiformis, which is the first molecular sequence reported for a xanthophycean alga. Evidence is provided for an independent and polyphyletic origin of plastids from five out of the six major taxa of photosynthetic eukaryotes. This conclusion is reached by comparing a plastid-based pattern of D1 similarity with a nucleus-based similarity pattern published recently. Furthermore, the availability of D1 sequences from five eukaryotic algae led to a re-evaluation of the taxonomic position of Prochlorothrix. 相似文献
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Juha-Matti Savola Michael Hill Mia Engstrom Hannele Merivuori Siegfried Wurster Steven G McGuire Susan H Fox Alan R Crossman Jonathan M Brotchie 《Movement disorders》2003,18(8):872-883
Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease. 相似文献
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Summary The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle.Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other.These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites. 相似文献
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