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31.
Steffens H Eek B Trudrung P Mense S 《Pflügers Archiv : European journal of physiology》2003,445(5):607-613
The properties of tetrodotoxin (TTX)-resistant C-fibre afferents of the dorsal roots were tested in Sprague-Dawley rats. Dorsal roots (L4-L6) were blocked with TTX (0.5-1 micro M) and the amplitude of the first response of the dorsal horn superficial interneurones (cord dorsum potential, CDP) to electrical stimulation of peripheral C-fibres in combination with natural noxious stimulation was taken as measure for intact conductivity of different kinds of noxious input by means of the C-fibre refractory period. After blockade of dorsal roots with TTX, formerly masked CDPs from muscle C-fibre afferents were uncovered. Noxious pressure to the gastrocnemius soleus muscle belly and noxious pinch to the calcanean tendon proved to be TTX resistant and therefore was propagated centrally. For cutaneous heat nociceptors it could also be shown that conductivity was intact after blockade of the dorsal roots with TTX. However, we could not exclude the TTX resistance of non-nociceptive receptors of muscle or skin. Nevertheless, blockade of afferents with TTX together with suitable stimulation techniques proves to be a reliable method to investigate central effects from C-fibre afferents without contaminating effects from A-fibres in the rat. 相似文献
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Udo Vanhoefer Mitra Tewes Federico Rojo Olaf Dirsch Norbert Schleucher Oliver Rosen Joachim Tillner Andreas Kovar Ada H Braun Tanja Trarbach Siegfried Seeber Andreas Harstrick José Baselga 《Journal of clinical oncology》2004,22(1):175-184
PURPOSE: To investigate the safety and tolerability and to explore the pharmacokinetic and pharmacodynamic profile of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with solid tumors that express epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: This was a phase I dose-escalation trial of EMD72000 in patients with advanced, EGFR-positive, solid malignancies that were not amenable to any established chemotherapy or radiotherapy treatment. EMD72000 was administered weekly without routine premedication until disease progression or unacceptable toxicity. RESULTS: Twenty-two patients were treated with EMD72000 at five different dose levels (400 to 2,000 mg/wk). National Cancer Institute common toxicity criteria grade 3 headache and fever occurring after the first infusion were dose limiting at 2,000 mg/wk; thus, the maximum-tolerated dose was 1,600 mg/wk. No other severe side effects, especially no allergic reactions or diarrhea, were observed. Acneiform skin reaction was the most common toxicity, but it was mild, with grade 1 in 11 patients (50%) and grade 2 in three patients (14%). Pharmacokinetic analyses demonstrated a predictable pharmacokinetic profile for EMD72000. Pharmacodynamic studies on serial skin biopsies revealed that EMD72000 effectively abrogated EGFR-mediated cell signaling (eg, reduced phosphorylation of EGFR and mitogen-activated protein kinase), with no alteration in total EGFR protein. Objective responses (23%; 95% CI, 8% to 45%) and disease stabilization (27%; 95% CI, 11% to 50%) were achieved at all dose levels, and responding patients received treatment for up to 18 months without cumulative toxicity. CONCLUSION: Treatment with EMD72000 was well tolerated and showed evidence of activity in heavily pretreated patients with EGFR-expressing tumors. EMD72000 at the investigated doses significantly inhibited downstream EGFR-dependent processes. 相似文献
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Cvirn G Cimenti C Kutschera J Ferstl U Wagner T Muntean W Jurgens G Gallistl S Koestenberger M 《European journal of pediatrics》2007,166(5):427-431
In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran
in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant
treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin.
We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by
means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time
to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately
the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC50) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l
vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights
in cord vs. adult plasma. Markedly lower concentrations (IC50) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l
vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress
thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic
therapy. 相似文献
38.
Three new isocoumarin derivatives ( 2- 4) were isolated together with monocerin ( 1) from Microdochium bolleyi, an endophytic fungus from Fagonia cretica, a herbaceous plant of the semiarid coastal regions of Gomera. Compounds 2 and 3 are both 12-oxo epimers of 1, and 4 is a ring-opened derivative of 1. The structures were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations were determined by a modified Mosher's method. Compounds 1, 3, and 4 showed good antifungal, antibacterial, and antialgal activities against Microbotryum violaceum, Escherichia coli, Bacillus megaterium, and Chlorella fusca. Compound 2 was moderately antifungal and antialgal. 相似文献
39.
David M. Goldenberg Helmut Schmidt Siegfried Witte 《Journal of cancer research and clinical oncology》1967,69(4):316-325
Zusammenfassung Das Wachstumsverhalten zweier in das Gehirn von Goldhamstern implantierter menschlicher Tumoren (H. Ad. Nr. 1 und H. S. Nr. 1) wurde untersucht. Bei allen Tieren konnte ein Tumorwachstum histologisch nachgewiesen werden. Cortisonvorbehandlung der Wirtstiere begünstigte bei H. Ad. Nr. 1 die Tumorausbreitung und führte frühzeitiger zum Tode. Das intracerebrale Tumorwachstum führte jedoch auch unabhängig von der Wirtsvorbehandlung bei allen Tieren zum Tode innerhalb von 4 Wochen nach der Transplantation. Beide Geschwulst-typen wuchsen am besten in den liquorhaltigen Räumen, weniger in der Hirnsubstanz. Die Bevorzugung der Meningen durch beide Tumortypen entspricht der allgemeinen Erfahrung über die cerebrale Metastasierung entdifferenzierte Sarkome und Adenocarcinome.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
Summary The growth behavior of two human tumors (H. Ad. No. 1 and H. S. No. 1) transplanted to the hamster brain has been studied. Tumor growth could be histologically verified in all animals inoculated. Cortisone-conditioning of the host increased tumor expansion and resulted in an earlier and more rapid death rate in the H. Ad. No. 1 group. Regardless of tumor or host-conditioning employed, all animals succumbed to intracerebral tumor growth by the end of the fourth week post transplantation. Both tumor types grew better in the ventricles and subarachnoid space than in the brain tissue itself. The predilection of these two tumor types for the meninges confirms our clinical knowledge on the pattern of cerebral metastasis of dedifferentiated sarcomas and adenocarcinomas.
Mit Unterstützung der Deutschen Forschungsgemeinschaft. 相似文献
40.
Ohne Zusammenfassung
Im Auszug vorgetragen von Dr. R. Kraus am IX. internat. Congresse für Hygiene und Demographie (Madrid April 1898). 相似文献