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11.
Itoh K Naganawa Y Matsuzawa F Aikawa S Doi H Sasagasako N Yamada T Kira J Kobayashi T Pshezhetsky AV Sakuraba H 《Journal of human genetics》2002,47(1):29-37
Three novel missense mutations in the human lysosomal sialidase gene causing amino acid substitutions (P80L, W240R, and P316S)
in the coding region were identified in two Japanese sialidosis patients. One patient with a severe, congenital form of type
2 sialidosis was a compound heterozygote for 239C-to-T (P80L) and 718T-to-C (W240R). The other patient with a mild juvenile-onset
phenotype (type 1) was a homozygote for the base substitution of 946C-to-T (P316S). None of these mutant cDNA products showed
enzymatic activity toward an artificial substrate when coexpressed in galactosialidosis fibroblastic cells together with protective
protein/cathepsin A (PPCA). All mutants showed a reticular immunofluorescence distribution when coexpressed with the PPCA gene in COS-1 cells, suggesting that the gene products were retained in the endoplasmic reticulum/Golgi area or rapidly degraded
in the lysosomes. Homology modeling of the structural changes introduced by the mutations predicted that the P80L and P316S
transversions cause large conformational changes including the active site residues responsible for binding the sialic acid
carboxylate group. The W240R substitution was deduced to influence the molecular surface structure of a limited region of
the constructed models, which was also influenced by previously identified V217M and G243R transversions.
Received: Stptember 21, 2001 / Accepted: November 2, 2001 相似文献
12.
T. Ebina A. Sato K. Umezu N. Ishida S. Ohyama A. Oizumi K. Aikawa S. Katagiri N. Katsushima A. Imai S. Kitaoka H. Suzuki T. Konno 《Medical microbiology and immunology》1985,174(4):177-185
After immunizing 8-month pregnant Holstein cows with human rotavirus, Wa strain, cow colostrum containing neutralizing antibody to human rotavirus, designated as Rota colostrum, was obtained. After randomly grouping 13 infants from a single orphanage, 6 infants received 20 ml of Rota colostrum every morning and 7 control infants received 20 ml of market milk. One month later, rotavirus associated diarrhea was observed in 6 of the 7 infants given milk and 1 out of the 6 infants given Rota colostrum. Orally administered Rota colostrum significantly protected infants from diarrhea caused by rotavirus (P < 0.05). Two out of 5 Rota colostrum recipients who were free from diarrhea showed rises in complement fixation (CF) antibody titer after the rotavirus infection epidemic. Thus, Rota colostrum prevented the outbreak of diarrhea but did not prevent immunological responses to natural rotavirus infection. In the therapeutic trial Rota colostrum had no effect on duration of diarrhea, bowel movements or virus shedding in stool. However, there were no side-effects of Rota colostrum. 相似文献
13.
14.
This study assessed the antimalarial activity of dipyridamole, a well-known vasodilator and inhibitor of platelet aggregation. Dipyridamole was effective against all of the erythrocytic stages such as rings, trophozoites and schizonts, and induced ultrastructural changes during the transition from trophozoite to schizont in vitro. Merozoites were also inhibited from invading dipyridamole-treated erythrocytes. It seems that dipyridamole binds to the erythrocyte membrane blocking the receptors for the merozoite. The 50% inhibitory concentration (IC(50)) of dipyridamole against Plasmodium falciparum infection was 30 nM. The IC(50) of chloroquine decreased from 97.0 nM to 13.7 nM when combined with dipyridamole (0.1 nM). Therefore, we suggest that dipyridamole has antiplasmodial activity due to its ability to arrest parasite development and by inhibiting merozoite invasion of the erythrocytes. Chloroquine activity against P. falciparum is also enhanced by the addition of dipyridamole. Treatment with a combination of chloroquine and dipyridamole may lead to a more effective treatment for chloroquine-resistant strains of P. falciparum. 相似文献
15.
Summary Suckling mice which received a single intraperitoneal injection of 6-aminonicotinamide on the 5th postnatal day, consistently developed hydrocephalus. During the early stages of hydrocephalus (7–9 days after injection), aqueductal lesions were characterized by edematous ependymal and subependymal cells, and spongy changes in the periaqueductal area, which resulted in aqueduct stenosis. Later stages (after 20 days post-injection) showed that these edematous changes totally subsided, leaving an obliterated aqueduct which was similar to that of human congenital hydrocephalus. At the completely obliterated area, ultrastructural investigation disclosed a normal-looking neuropil but no aqueductal lumen. In the remaining ependymal cell, increased intermediate filaments and lipid droplets occurred. These data suggest that acute ependymal cell degeneration during the perinatal period may result in the profile of aqueduct agenesis in human congenital hydrocephalus.Supported in part by research grants NS-03356, NS-10803 from NINCDS, USPHS 相似文献
16.
Nagasaka H Nakajima T Takano Y Sato I Aikawa K Matsumoto N Matsumoto I Hori T 《Journal of anesthesia》1990,4(2):102-109
The effects of enflurane (0.5%, 1.5% and 2.5%) on the excitation and inhibition of dorsal horn wide dynamic range (WDR) neuronal activity induced by bradykinin (BK) injection was studied in spinal cats. Extracellular activity was recorded in the dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli applied to the cutaneous receptive fields on the left hind paw foot pads of decerebrate, spinal cord transected (L1–2) cats. When 10µg of BK was injected into the femoral artery ipsilateral to the recording site as the noxious test stimulus, 24 of 26 WDR neurons (92%) gave excitatory responses and 2 (8%) gave inhibitory resposes. On the other hand, when the injection of 10µg of BK into the femoral artery contralateral to the recording site was used as the noxious test stimulus, 7 of 12 WDR neurons (58%) gave inhibitory responses, 3 (25%) gave excitatory responses, and 2 (17%) showed no response. The excitatory neuronal activity in WDR neurons was not depressed by 0.5% or 1.5% enflurane but was depressed significantly by 2.5%. However, the inhibitory neuronal activity in WDR neurons was significantly depressed by 0.5%, 1.5% and 2.5% enflurane. We have found that enflurane reduces the excitation as well as the inhibition of dorsal horn WDR neuronal activity induced by BK injection. These results suggest that the reduction of excitatory and inhibitory responses produced by noxious stimulation is likely to be the fundamental basis of the enflurane-induced anesthetic state in terms of WDR neurons.(Nagasaka H, Nakajima T, Takano Y et al.: Enflurane reduces the excitation and inhibition of dosal horn WDR neuronal activity induced by BK injection in spinal cats. J Anesth 4: 102–109, 1990) 相似文献
17.
Miyagi M Sakai K Hasegawa A Ohara T Mizuiri S Aikawa A Hadano T Nakano H Shindo M Ishikawa Y Hasegawa C Hirayama N Arai K 《Clinical transplantation》1999,13(Z1):43-47
A 41-yr-old patient with non-insulin-dependent diabetes mellitus (NIDDM), before and after ABO-incompatible renal transplant, is reviewed using serial protocol biopsy. Although she recovered from delayed hyperacute rejection (DHAR) immediately post-transplantation, her graft function deteriorated gradually. A mild acute transplant glomerulitis, noted at the 155th day post-transplantation, progressed to pronounced chronic transplant glomerulopathy over 5 yr. In the specimen of the last biopsy, at 5 yr post-transplantation, glomeruli demonstrated an exudative hyaline lesion, which was characteristic of diabetic nephropathy in addition to chronic transplant glomerulopathy. Therefore, we made a diagnosis of this glomerular lesion as chronic transplant glomerulopathy complicated by diabetic glomerulopathy. Considering the result of this case, the protocol biopsy is a useful procedure to diagnose an accurate cause of graft dysfunction in individual cases. It is concluded that the protocol biopsy is apparently useful for the detection of various pathological processes occurring in allograft and may contribute to a strategy for improvement of graft survival. 相似文献
18.
K Aikawa Y Sato T Furuchi M Ikemoto Y Fujimoto H Arai K Inoue 《Biochemical pharmacology》1999,58(3):447-453
Cultured macrophages take up and metabolize cholesterol-containing liposomes, resulting in massive accumulation of cholesteryl esters in the cells. Using this system, the effects of azole antimycotics on cholesteryl ester formation were studied. Incubation of mouse peritoneal macrophages with ketoconazole, miconazole, or econazole (0.1-10 microM) resulted in concentration-dependent inhibition of cholesteryl ester synthesis from endocytosed cholesterol. IC50 values (concentration resulting in 50% inhibition) were 1.4 +/- 0.1 microM, 4.1 +/- 0.2 microM, and 3.6 +/- 0.2 microM for ketoconazole, miconazole, and econazole, respectively. Complete inhibition was observed with 10 microM ketoconazole, and miconazole and econazole, each at 10 microM, caused 70 and 75% inhibition, respectively, of cholesteryl ester synthesis. The mechanism underlying the inhibition by ketoconazole was further studied. Ketoconazole did not appreciably block the uptake of liposomes or formation of triacylglycerol up to 10 microM. Interestingly, ketoconazole suppressed only 30% of 25-hydroxycholesterol-induced endogenous cholesterol esterification under conditions where esterification of endocytosed cholesterol was completely inhibited. Cytochemical studies with filipin-cholesterol staining revealed that ketoconazole induced massive accumulation of endocytosed cholesterol in macrophage phagolysosomes. These results indicate that ketoconazole inhibits cholesteryl ester formation in macrophages by blocking the intracellular transport of endocytosed cholesterol from lysosomes to the endoplasmic reticulum. 相似文献
19.
Pregnant rats were given 0%-, 5%-, 10%- and 20% ethyl alcohol in drinking water during the gestation period.We evaluated the brain function of pups born of alcohol-administered dams. Learning ability (Sidman avoidance behavior), the amounts of monoamines (noradrenalin, dopamine, serotonin) and metabolites (3,4-dihydroxyphenyl acetic acid [DOPAC], homovanillic acid [HVA] and 5-hydroxyindole acetic acid [5-HIAA])in whole brain were examined for neurobehavioral and neurochemical effects.There was no effect on Sidman avoidance behavior in 56-day-old offspring, but alterations of the amounts of monoamines and their metabolites were observed even in 66-day-old offspring as a result of the dams' exposure to ethanol during pregnancy. 相似文献
20.
The Merkel cell is a distinctive nondendritic, nonkeratinocytic, epithelial clear cell believed to migrate from the neural crest to the epidermis and dermis, which is usually located in or near the basal layer of the epidermis and associated with nerve terminations. Merkel first described these cells in 1875 as "Tastzellen" occurring in the snout of a mole. They are believed to function as slowly adapting mechanoreceptors that mediate the sense of touch. Tumors arising from Merkel cells have been reported to occur on the head and neck area, the trunk, arms, and legs, and resemble a primary cutaneous lymphoma or cutaneous metastasis of a lymphoma or a carcinoma. Electron microscopy, to locate the characteristic membrane-bound, dense core neurosecretory granules, is needed for accurate diagnosis. These tumors must be treated aggressively to minimize the chance of local recurrence and nodal or visceral metastases. The authors present a case of Merkel cell tumor occurring on the eyelid. The clinical history, light and electron microscopic findings are shown. 相似文献