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191.
192.
The effect of interleukin 4 (IL-4) on expression of antitumor activity of blood monocytes purified by counter-flow centrifugal elutriation from healthy donors was examined. The blood monocytes were incubated for 24 h in medium with lipopolysaccharide, interferon γ (IFN-γ) or desmethyl muramyl dipeptide (norMDP) or with IFN-γ and norMDP in the presence of IL-4, and then their tumoricidal activity was assayed by measuring 125 IUdR release from human melanoma (A375) cells. Irrespective of activation stimulus, addition of IL-4 to cultures of monocytes and activators resulted in dose-dependent suppression of the tumoricidal activity of monocytes against parent A375 melanoma cells and the variant cells, A375-R resistant to IL-1 and tumor necrosis factor α. IL-4 suppressed the early induction phase of monocyte activation. Rabbit anti-IL-4 antisera completely blocked the IL-4-mediated suppression of monocyte activation to the tumoricidal state. These findings suggest that IL-4 is important in vivo in down-regulation of anti-tumor expression of monocytes. 相似文献
193.
Lithium Concentration in Cerebrospinal Fluid of Affective Psychotic Patients Treated with Lithium Carbonate and its Clinical Response 总被引:1,自引:1,他引:0
194.
195.
Neural responses to several chemicals of the pit organs and terminal buds on the facial skin of the carp were compared electrophysiologically. Nerve inpulses from the pit organs were larger than those from the terminal buds. The pit organs were more sensitive to salts and especially acids than the terminal buds. The former did not respond to sucrose, silk worm pupa extract, betaine and amino acids except acidic ones. The latter, however, responded well to them. 相似文献
196.
Hideo Yamane M.D. Nobukatsu Katoh M.D. Naosuke Tani M.D. Norihumi Iwase M.D. Saburo Takahashi M.D. Hiroshi Haga Tatsuo Abe M.D. 《Psychiatry and clinical neurosciences》1977,31(2):167-171
A case of Gilles de la Tourette's syndrome with alcoholism and migraine is described. Multiple motor tics and coprolalia were suppressed by the treatment with haloperidol. The concentrations of HVA and 5–HIAA in the cerebrospinal fluid were measured and increment of HVA concentrations was outstanding while his symptoms were aggravated. This might be evidence for hyperactivity of dopaminergic neurons involved in manifest symptomatology of this syndrome. 相似文献
197.
Current status and perspective of angiogenesis and antivascular therapeutic strategy: non-small cell lung cancer 总被引:4,自引:0,他引:4
Yano S Matsumori Y Ikuta K Ogino H Doljinsuren T Sone S 《International journal of clinical oncology / Japan Society of Clinical Oncology》2006,11(2):73-81
Lung cancer is the leading cause of cancer death worldwide, and most patients die of metastatic disease. Angiogenesis, namely,
neovascularization from preexisting vasculature, is necessary for tumor growth in both primary and distant organs to supply
oxygen and nutrition. Angiogenesis consists of sprouting and nonsprouting (the enlargement, splitting, and fusion of preexisting
vessels) processes, and both can occur concurrently. The growth of non-small cell lung cancer (NSCLC), which accounts for
more than 80% of all lung cancers, is usually dependent on angiogenesis, which is regulated by complex mechanisms in the presence
of various angiogenesis-related molecules. Vascular endothelial growth factor (VEGF), also known as vascular permeability
factor (VPF), is one of the most potent angiogenic molecules, while also regulating both angiogenesis and vascular permeability
and hence promoting tumor progression and the development of malignant pleural effusions in NSCLC. Recent clinical trials
showed that the anti-VEGF antibody bevacizumab, combined with standard first-line chemotherapy, provided a statistically and
clinically significant survival advantage with tolerable toxicity. In addition, the combined use of the anti-VEGF antibody
with an inhibitor of epidermal growth factor receptor (EGFR) has also shown favorable antitumor efficiency. These successes
proved the validity of an antivasculature strategy for NSCLC. Furthermore, a large number of antivasculature agents have been
shown to be effective against multiple targets. The efficiency of these compounds is currently being investigated in clinical
trials for NSCLC. 相似文献
198.
Nakataki E Yano S Matsumori Y Goto H Kakiuchi S Muguruma H Bando Y Uehara H Hamada H Kito K Yokoyama A Sone S 《Cancer science》2006,97(3):183-191
Malignant pleural mesothelioma (MPM) is closely related to exposure to asbestos, and a rapid increase in the number of MPM patients in Japan is estimated in the years 2010-2050. The purpose of the present study was to establish a clinically relevant animal model that shows human patient-like progression of MPM. Here, we demonstrate that a human MPM cell line (EHMES-10) inoculated orthotopically (thoracic cavity) into severe combined immunodeficiency (SCID) mice produces highly vascularized thoracic tumors with pleural dissemination and bloody pleural effusions by 5 weeks, suggesting a patient-like progression of this cell line after orthotopic inoculation. EHMES-10 cells overexpressed vascular endothelial growth factor (VEGF), a molecule responsible for malignant effusions, and its receptor. Treatment with cisplatin, but not gemcitabine, significantly inhibited the production of pleural effusions, but it was not effective for thoracic tumors, consistent with chemotherapy refractory characteristics of MPM in patients. Our patient-like orthotopic model using EHMES-10 cells overexpressing VEGF and its receptor may be useful for examining the molecular pathogenesis of MPM and may contribute to the development of novel treatment strategies for MPM. 相似文献
199.
Nishimori I Minakuchi T Morimoto K Sano S Onishi S Takeuchi H Vullo D Scozzafava A Supuran CT 《Journal of medicinal chemistry》2006,49(6):2117-2126
We have cloned and sequenced Helicobacter pylori alpha-class carbonic anhydrase (hpCA) from patients with different gastric mucosal lesions, including gastritis (n=15), ulcer (n=6), and cancer (n=16). Although several polymorphisms were newly identified such as 12Ala, 13Thr, 16Ile, and 168Phe, there was no significant relevance of any polymorphism with gastric mucosal lesion types. A library of sulfonamides/sulfamates has been investigated for the inhibition of hpCA, whereas new derivatives have been obtained by attaching 4-tert-butyl-phenylcarboxamido/sulfonamido tails to benzenesulfonamide/1,3,4-thiadiazole-2-sulfonamide scaffolds. All types of activity for inhibition of hpCA have been detected. Dorzolamide and simple 4-substituted benzenesulfonamides were weak inhibitors (KI 873-4360 nM). Sulfanilamide, orthanilamide, some of their derivatives, and indisulam showed better activity (KI 413-640 nM), whereas most of the clinically used inhibitors, such as methazolamide, ethoxzolamide, dichlorophenamide, brinzolamide, topiramate, zonisamide, etc., acted as medium-potency inhibitors (KI 105-378 nM). Some potent hpCA inhibitors were detected too (KI 12-84 nM) among acetazolamide, 4-amino-6-chloro-1,3-benzenedisulfonamide and some newly designed compounds incorporating lipophilic tails. Some of the newly prepared derivatives had selectivity ratios for inhibiting hpCA over hCA II in the range of 1.25-3.48, showing thus some selectivity for inhibiting the bacterial enzyme. Since hpCA is essential for the survival of the pathogen in acid, it might be used as a new pharmacologic tool in the management of drug-resistant H. pylori. 相似文献
200.
Ali N Yoshizumi M Yano S Sone S Ohnishi H Ishizawa K Kanematsu Y Tsuchiya K Tamaki T 《Journal of pharmacological sciences》2006,102(1):112-120
M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring molecules such as beta-catenin. Here, we examined the effect of M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The findings reveal pretreatment with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin phosphorylation. However, M475271 significantly increases VE-cadherin and beta-catenin association compared to the VEGF-treated group. Confocal laser microscopic examination confirmed the augmentation effect of M475271 on VE-cadherin and beta-catenin association. Finally, M475271 was shown to have inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced HUVEC proliferation, migration, and tube formation. These findings suggest that M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction stability. Although the involvement of other signaling molecules cannot be ruled out, M475271 has potential as a drug for the inhibition of the angiogenesis needed for tumor growth and metastasis. 相似文献