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排序方式: 共有338条查询结果,搜索用时 31 毫秒
41.
Takahashi A Hasegawa M Sumazaki R Suzuki M Toki F Suehiro T Onigata K Tomomasa T Suzuki T Matsui A Morikawa A Kuwano H 《European journal of gastroenterology & hepatology》2007,19(11):942-946
OBJECT: The authors report the case of a boy with PFIC type 2 or BRIC type 2 who suffered from liver dysfunction at 2 months after birth. METHODS AND RESULTS: A liver biopsy specimen revealed mild liver cirrhosis, and the findings resembled those observed in Byler disease. Genetic examination revealed a normal familial intrahepatic cholestasis-1 gene, but a heterozygous mutation for the ABCB11, C1620A (F540L), was observed. Therefore, the patient was initially diagnosed with PFIC type 2. For 3 years after the diagnosis, he had severe pruritus, an increased serum bile acid, and normal serum values of gamma-glutamyl transaminase. At the age of 2, treatment with administration of ursodeoxycholic acid was started; subsequently, a gradual improvement in his liver function was observed. At the age of 3, he suffered from massive intestinal and pulmonary hemorrhage, which improved immediately after the administration of vitamin K. He was then admitted to our hospital for liver transplantation. At 1 month after the admission, his liver dysfunction showed further improvement, except for a mild increase in the serum bile acid level. This condition did not show any change during the 5-year follow-up period. In addition, the patient showed severe growth failure and was diagnosed with growth hormone deficiency. Hence, he receives growth hormone administration. CONCLUSION: The patient could be genetically diagnosed with bile salt export pump disease of PFIC type 2 or BRIC type 2. Various clinical features are observed in PFIC or BRIC patients with ABCB11 mutation. 相似文献
42.
Masafumi Horie Ichiro Sekiya Tomomasa Nakamura Hozumi Tanaka Kotaro Maekawa Masaru Nakanishi Takeshi Muneta Eiji Kobayashi 《Biopharmaceutics & drug disposition》2009,30(4):204-208
To evaluate the pharmacokinetics of topical drugs, in vitro permeation studies are performed using sacrificed pig skin or human tissues resected at surgery; however, these methods have their limitations in in vivo pharmacokinetics. This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24 h, followed by sequential collection of blood specimens from 0 to 36 h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12 h after the application (n=4). Ketoprofen was first detected in the plasma at 8 h, the concentration increasing up to 24 h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprofen concentrations in the tissues decreased with increasing depth of the tissues, but the values in the deep muscles, being the lowest among the tissues examined, were still higher than those in the plasma. While the data of drug concentration in human tissue are difficult to test, the Mexican hairless pig model appears to be attractive for in vivo pharmacokinetic studies of topically applied ketoprofen. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
43.
P. GIL‐BERNABE C. N. D'ALESSANDRO‐GABAZZA M. TODA D. BOVEDA RUIZ Y. MIYAKE T. SUZUKI Y. ONISHI J. MORSER E. C. GABAZZA Y. TAKEI Y. YANO 《Journal of thrombosis and haemostasis》2012,10(3):337-346
Summary. Background: Activated protein C (APC) can regulate immune and inflammatory responses and apoptosis. Protein C transgenic mice develop less diabetic nephropathy but whether exogenous administration of APC suppresses established diabetic nephropathy is unknown. Objectives: We investigated the therapeutic potential of APC in mice with streptozotocin‐induced diabetic nephropathy. Methods: Diabetes was induced in unilaterally nephrectomized C57/Bl6 mice using intraperitoneal (i.p.) injection of streptozotocin. Four weeks later, the mice were treated with i.p. exogenous APC every other day for 1 month. Results: APC‐treated mice had a significantly improved blood nitrogen urea‐to‐creatinine ratio, urine total protein to creatinine ratio and proteinuria, and had significantly less renal fibrosis as measured by the levels of collagen and hydroxyproline. The renal tissue concentration of monocyte chemoattractant protein‐1 (MCP‐1), vascular endothelial growth factor (VEGF) and the RNA expression of platelet‐derived growth factor (PDGF), transforming growth factor‐β1 and connective tissue growth factor (CTGF) were significantly lower in APC‐treated mice than in untreated animals. The percentage of apoptotic cells was reduced and the expression of podocin, nephrin and WT‐1 in the glomeruli was significantly improved in mice treated with APC compared with untreated mice. The levels of coagulation markers were not affected by APC treatment. Conclusion: Exogenous APC improves renal function and mitigates pathological changes in mice with diabetic nephropathy by suppressing the expression of fibrogenic cytokines, growth factors and apoptosis, suggesting its potential usefulness for the therapy of this disease. 相似文献
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BackgroundRecently, Achromobacter xylosoxidans has been related to chronic lung diseases in patients suffering from cystic fibrosis (CF), but its involvement has not been elucidated. Some virulence properties of A. xylosoxidans isolated from Brazilian patients with CF were revealed in this work.MethodsThis study examined the production of a cytotoxic factor of A. xylosoxidans capable of stimulating the secretion of inflammatory cytokines (IL-6 and IL-8) from lung mucoepidermoid carcinoma cells (NCI-H292). The cytokines were measured using enzyme-linked immunosorbent (ELISA) assays. To investigate whether the cytotoxic factors may be endotoxins, they were treated with polymyxin B.ResultsThe culture supernatants of all A. xylosoxidans produced a heat stable, active cytotoxin in NCI-H292 cells capable of leading to intracellular vacuoles and subsequent cell contact loss, chromatin condensation, a picnotic nucleus and cell death. There was a higher concentration of proinflammatory cytokines in the NCI-H292 cells after 24 h of incubation, with the fraction greater than 50 kDa from the culture supernatant. The cytotoxin activity remained even after treatment with polymyxin B, which suggested that the release of IL-6 and IL-8 was not stimulated by lipopolysaccharide (LPS).ConclusionThe cytotoxic factor produced by A. xylosoxidans may represent an important virulence factor, which when associated with CF chronic lung inflammation, may cause tissue damage and decline of lung function. 相似文献
47.
Takahashi A Tomomasa T Kaneko H Hatori R Ishige T Suzuki M Mochiki E Morikawa A Kuwano H 《Journal of gastroenterology》2005,40(11):1043-1048
Background We recorded in vivo colonic motility in rats with a deficiency of interstitial cells of Cajal (ICC) (Ws/Ws rats) and in wild-type rats (+/+ rats), with special reference to the effects of nitric oxide (NO) on colonic motility in
both types of rats, in order to ascertain the role of ICC in colonic motility, and the relationship between NO and ICC in
regard to colonic motility.
Methods Miniature strain-gauge force transducers were sutured on the surface of the ascending and sigmoid colon of Ws/Ws rats and +/+ rats as controls. After 1 week and a fasting period of 24 h, colonic motility in +/+ and Ws/Ws rats was recorded. We also studied the effect of NO on colonic motility in both types of rats, by means of the administration
of N-nitro-l-arginine methyl ester (l-NAME) or l-arginine.
Results In +/+ rats, there were contractions with high amplitude and long duration in both the ascending and sigmoid colon. The number,
amplitude, and duration of contractions in the ascending colon were 9.9/20 min, 6.1 g, and 22.7 s, respectively. These findings
in the sigmoid colon were 5.2/20 min, 5.2 g, and 23.0 s, respectively. The number of contractions in the ascending and sigmoid
colon in Ws/Ws rats (2.3 and 1.0/20 min) was significantly lower than that in +/+ rats (P < 0.05). The number of contractions in the ascending and sigmoid colon in +/+ rats (9.7 and 5.1/20 min before treatment)
was significantly increased by l-NAME administration (28.7 and 13.9/40–60 min after treatment; P < 0.05), but that in Ws/Ws rats was not influenced. The number of contractions in the ascending and sigmoid colon in +/+ rats (10.2 and 5.2/20 min before
treatment) was significantly decreased by l-arginine administration (3.6 and 2.1/40–60 min after treatment; P < 0.05), but that in Ws/Ws rats was not influenced.
Conclusions ICC must be related to the occurrence of a normal number of colonic contractions. NO may be involved in the inhibitory regulation
of colonic motility, and the effect of NO on the occurrence of contractions appears to be mediated by ICC. 相似文献
48.
Dr. T. Tomomasa T. Kuroume H. Arai K. Wakabayashi Z. Itoh 《Digestive diseases and sciences》1986,31(2):157-161
Fifteen healthy subjects, fasted at least 8 hr, were studied by means of an infused manometric method. Twenty minutes after termination of the natural phase III activity in the duodenum, erythromycin or normal saline was administered intravenously for 15 min. When normal saline (N = 5) was infused, the next migrating motor complex (MMC) was initiated 151.2 +/- 42.1 min after the infusion. On the other hand, when erythromycin was infused at a rate of 1.0 mg/kg/hr (N = 5) or 3.0 mg/kg/hr (N = 5), MMC-like contractions were initiated at shorter intervals, ie, 47.8 +/- 40.9 min (P less than 0.005) or 23.0 +/- 13.0 min (P less than 0.001) respectively. The duration, frequency, amplitude, and migrating velocity of the naturally occurring MMC (N-MMC) were not significantly different from those of the erythromycin-induced contractions except for the duration of the phase III contractions in the stomach; the duration (5.3 +/- 2.2 min) of the erythromycin-induced contractions being significantly (P less than 0.05) longer than that (3.2 +/- 0.9 min) of the naturally occurring MMC. The immunoreactive motilin (IRM) concentration did not increase significantly after the infusion of erythromycin, when compared to that after infusion of normal saline. It is concluded that erythromycin at a dose of 1-3 mg/kg/hr for 15 min during the interdigestive state, similar to motilin, has a significant influence upon the initiation of MMC in the human gastrointestinal tract, but further investigations are required to confirm whether endogenous motilin is involved or not. 相似文献
49.
Norimasa Arita Mitsuko R Ito Kimihiko Nakatani Hiroshi Fujii Hisashi Ohishi Tomomasa Izumiyama Yasuhiko Hirabayashi Terunobu Saito Masato Nose 《Ryūmachi》2002,42(3):597-604
We describe a case of a 61-year-old woman with amyopathic dermatomyositis (ADM), who developed rapidly progressive interstitial pneumonia and died of respiratory failure. An autopsy revealed interstitial pneumonia with diffuse alveolar damage, associated with infiltration of T cells, mostly positive for CD 8. The alveolar lining epithelial cells manifested the remarkable expression of immediate early/early antigen of human cytomegalovirus (HCMV). Moreover, the extract of the lung was transmittable of HCMV infection to cultured human embryo-fibroblasts in vitro. On the other hand, in the semi-quantitative analysis of HCMV genome, using laser-assisted microdissection, followed by PCR method, the genomic DNA in the alveolar lining epithelial cells was little detected in this case, although it was remarkable in the case of immunodeficiency with cytomegalovirus pneumonia. This case may be important to know the role of the immune response of host to HCMV infection on the development of rapidly progressive interstitial pneumonia. 相似文献
50.
Tomomasa T Kobayashi A Kaneko H Mika S Maisawa S Chino Y Syou H Yoden A Fujino J Tanikawa M Yamashita T Kimura S Kanoh M Sawada K Morikawa A 《Digestive diseases and sciences》2003,48(4):750-754
Granulocytapheresis (GCAP) has produced efficacy in adult patients with ulcerative colitis (UC) by adsorbing activated granulocytes and monocytes/macrophages. We retrospectively investigated efficacy and safety of GCAP in pediatric patients with active UC. Twelve steroid-refractory children (12.2±3.1 years old) were treated with GCAP, one session/week for 5–10 consecutive weeks. In 8 patients, clinical symptoms improved after two GCAP sessions. Normal body temperature, stool frequency, and disappearance of blood in stool were seen after 24.3±11.5 days. The endoscopic grade improved from 2.6±0.3 to 0.4±0.2. One patient who initially responded, developed bloody diarrhea later and 2 cases remained unchanged. The dose of steroid was tapered during GCAP therapy by 50%. No serious adverse effects were noted. Four of 8 cases relapsed 3.5 ± 2.2 months after the last GCAP while on maintenance therapy, the other 4 were in remission up to 22.8±18.1 months. In conclusion, GCAP appears to be effective and well tolerated in children with steroid-refractory UC. 相似文献