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91.
Yasuhiko Kano Miyuki Akutsu Saburo Tsunoda Koyoshi Mori Kenichi Suzuki Ken-Ichi Adachi 《Cancer chemotherapy and pharmacology》1998,42(2):91-98
Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for
use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to
its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in
four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects
of drug combinations at the IC80 level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic
(subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon
cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel
for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings
suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic
combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist
in determining the optimal schedule for this combination in clinical use.
Received: 25 February 1997 / Accepted: 6 November 1997 相似文献
92.
Akio Hiraki Hiroshi Ueoka Toshihiko Matsuo Tomio Nakagawa Tadashi Yoshino Katsuyuki Kiura Masahiro Tabata Katsuyoshi Sakae Yuji Ohtsuki Yoshio Hiraki Mine Harada 《International journal of clinical oncology / Japan Society of Clinical Oncology》1998,3(3):186-190
A 72-year-old Japanese woman, suffering from squamous cell lung cancer with brain metastasis, underwent 2 courses of combination
chemotherapy, consisting of cisplatin and vindesine. Although both the primary tumor and the brain metastasis regressed markedly,
she developed left ocular pain with blurred vision. An abnormal mass was found in the left iris, and cytologic examination
of the aqueous aspirate revealed a few malignant cells, which, when examined by electron microscopy, were considered to be
derived from squamous cell carcinoma of the lung. 相似文献
93.
Matsumoto H Hayashi S Hatashita M Shioura H Ohtsubo T Kitai R Ohnishi T Yukawa O Furusawa Y Kano E 《International journal of radiation biology》2000,76(12):1649-1657
PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions. 相似文献
94.
Shinji Ohmori Yasuo Ohno Tadashi Makino Toshio Kashihara 《European journal of pharmaceutics and biopharmaceutics》2005,59(2):289-297
The purpose of this study was to apply an electronic nose system for evaluation of unpleasant odor in tablets containing L-cysteine, an unpleasant odor drug, and demonstrate the odor masking ability of thin-layer sugarless coated tablets, which we have newly developed, by both electronic nose system and sensory evaluations. We demonstrated the qualitative evaluation of the unpleasant odor using air as a reference indicator and the quantitative evaluation of the unpleasant odor using the distances between air and samples in the electronic nose system evaluation. The electronic nose system evaluation was positively and well-correlated with the sensory evaluation by volunteers. We suggest that the electronic nose system evaluation is appropriate as an alternative or a support method for sensory evaluation by volunteers. As the results of both electronic nose system and sensory evaluations, we demonstrated that the thin-layer sugarless coated tablets have excellent masking ability of the unpleasant odor, equivalent to that of sugar-coated tablets due to the dense coating layers. 相似文献
95.
No Improvement of Adult Height in Non-growth Hormone (GH) Deficient Short
Children with GH Treatment
Toshiaki Tanaka Kenji Fujieda Susumu Yokoya Akira Shimatsu Katsuhiko Tachibana Hiroyuki Tanaka Takakuni Tanizawa Akira Teramoto Toshiro Nagai Yoshikazu Nishi Yukihiro Hasegawa Kunihiko Hanew Keinosuke Fujita Reiko Horikawa Goro Takada Masao Miyashita Tadashi Ohno Kazuo Komatsu 《Clinical Pediatric Endocrinology》2006,15(1):15-21
It is still in doubt whether the standard-dose growth hormone (GH) used in Japan (0.5
IU/kg/week, 0.167 mg/kg/week) for growth hormone deficiency is effective for achieving
significant adult height improvement in non-growth hormone deficient (non-GHD) short
children. We compared the growth of GH-treated non-GHD short children with that of
untreated short children to examine the effect of standard-dose GH treatment on non-GHD
short children. GH treatment with recombinant human growth hormone (rhGH) was started
before the age of 11 yr in 64 boys and 76 girls with non-GHD short stature registered at
the Foundation for Growth Science who have now reached their adult height. In 119
untreated boys and 127 untreated girls whose height standard deviation score (SDS) was
below –2 SD at the age of 6 yr, height growth was followed until 17 yr. Height SDS was
significantly lower before GH treatment in the GH-treated group than at the age of 6 yr in
the untreated group, in both sexes. Adult height and adult height SDS were significantly
greater in the untreated group than in the GH-treated group, in both sexes, although the
change in height SDS did not differ significantly. Height SDS was significantly lower
before GH treatment in the GH-treated group than at the age of 6 yr in the untreated
group, so 57 boys and 57 girls whose height SDS at the age of 6 yr in the untreated group
closely matched the height SDS before GH treatment in the GH-treated group were chosen for
comparison. Height SDS did not differ significantly between the GH-treated group before GH
treatment and the untreated group at the age of 6 yr, nor were there differences between
these subgroups in adult height, adult height SDS, or height SDS change, in either sex.
The effect of GH treatment is reported to be dose-dependent and doses over 0.23 mg/kg/week
are reported to be necessary to improve adult height in non-GHD short children. Currently,
the GH dose is fixed at 0.175 mg/kg/week in Japan, and we expected to find, and indeed
concluded, that ordinary GH treatment in Japanese, non-GHD short children does not improve
adult height. 相似文献
96.
Sung Yeon Kim Y R Santosh Laxmi Naomi Suzuki Kenichiro Ogura Tadashi Watabe Michael W Duffel Shinya Shibutani 《Drug metabolism and disposition》2005,33(11):1673-1678
Tamoxifen (TAM) is used as the standard endocrine therapy for breast cancer patients and as a chemopreventive agent for women at high risk for this disease. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Formation of TAM-DNA adducts in rat liver correlates with the development of hepatocarcinoma. TAM-DNA adducts are proposed to be formed through O-sulfonation and/or O-acetylation of alpha-hydroxylated TAM and its metabolites. However, the role of O-sulfonation and O-acetylation in the formation of TAM-DNA adducts has not been extensively investigated. Rat or human hydroxysteroid sulfotransferases (HST), acetyltransferases, and liver cytosol were incubated with calf thymus DNA, alpha-OHTAM, and either 3'-phosphoadenosine 5'-phosphosulfate (PAPS) or acetyl coenzyme A (acetyl-CoA) as a cofactor and analyzed for TAM-DNA adduct formation, using 32P postlableling/polyacrylamide gel electrophoresis analysis. TAM-DNA adduct was formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced using human N-acetyltransferase I and II. HST antibody inhibited approximately 90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that HST is primarily involved in the formation of TAM-DNA adducts. The formation of TAM-DNA adducts with rat liver cytosol and HST was much higher than that of human liver cytosol and HST. Our results indicate that TAM-DNA adducts are formed via O-sulfonation, not O-acetylation, of alpha-hydroxylated TAM and its metabolites. 相似文献
97.
98.
Dihydropyrimidine dehydrogenase activity in 150 healthy Japanese volunteers and identification of novel mutations. 总被引:4,自引:0,他引:4
99.
100.
Hiraki T Hamada N Kano T Isamoto Y 《Masui. The Japanese journal of anesthesiology》2000,49(5):535-539
We conducted hemodilutional autotransfusion using a closed circuit combined with a cell washing reinfusing system (Cell Saver) for two surgical patients of Jehovah's Witness. One was a 12 yr-old boy for extirpation of the teratoma in the anterior mediastinum and another was a 44 yr-old woman for left total hip replacement. The patients and their relatives had consented to the use of blood substitutes, hemodilutional autotransfusion using a closed circuit and Cell Saver. We devised a closed circuit system for hemodilutional autotransfusion combined with Cell Saver, in which two pumps for blood transfusion were used; one was for drawing blood from the femoral or the internal jugular vein and the other for returning blood to the peripheral vein. Blood volume in a bag interposed in the closed circuit was easily controlled by adjusting the speed of each pump. Blood collected from the surgical field by Cell Saver was also led to the bag. Acid citrate dextrose solution was infused into the closed circuit from the site close to the blood drawing. Both of our surgical patients were safely managed without homologus blood transfusion, although there remained some problems concerning the use of anticoagulants. 相似文献