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排序方式: 共有313条查询结果,搜索用时 31 毫秒
31.
TZT-1027, an Antimicrotubule Agent, Attacks Tumor Vasculature and Induces Tumor Cell Death 总被引:1,自引:0,他引:1
Masashi Otani Tsugitaka Natsume Jun-ichi Watanabe Motohiro Kobayashi Masanori Murakoshi Takashi Mikami Takaharu Nakayama 《Cancer science》2000,91(8):837-844
TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy. 相似文献
32.
Efficacy of transfusion with fresh‐frozen plasma:red blood cell concentrate ratio of 1 or more for amniotic fluid embolism with coagulopathy: a case–control study
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33.
Yang M Yamamoto H Kurashima H Takeuchi H Yokoyama T Tsujimoto H Kawashima Y 《European journal of pharmaceutical sciences》2012,46(5):374-380
Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion(TM) technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs. 相似文献
34.
Honda K Zheng N Murakoshi H Hashimoto M Sakai K Borghan MA Chikata T Koyanagi M Tamura Y Gatanaga H Oka S Takiguchi M 《European journal of immunology》2011,41(1):97-106
HIV-1 mutants escaping from HLA-A- or HLA-B-restricted CTL have been well studied, but those from HLA-C-restricted CTL have not. Therefore we investigated the ability of HLA-C-restricted CTL to select HIV-1 escape mutants. In the present study, we identified two novel HLA-Cw(*) 1202-restricted Pol-specific CTL epitopes (Pol328-9 and Pol463-10). CTL specific for these epitopes were detected in 25-40% of chronically HIV-1-infected HLA-Cw(*) 1202(+) individuals and had strong abilities to kill HIV-1-infected cells and to suppress HIV-1 replication in vitro, suggesting that these CTL may have the ability to effectively control HIV-1 in some HLA-Cw(*) 1202(+) individuals. Sequence analysis of these epitopes showed that a V-to-A substitution at the 9th position (V9A) of Pol 463-10 was significantly associated with the HLA-Cw(*) 1202 allele and that the V9A mutant was slowly selected in the HLA-Cw(*) 1202(+) individuals. Pol 463-10-specific CTL failed both to kill the V9A virus-infected cells and to suppress replication of the V9A mutant. These results indicate that the V9A mutation was selected as an escape mutant by the Pol463-10-specific CTL. The present study strongly suggests that some HLA-C-restricted CTL have a strong ability to suppress HIV-1 replication so that they can select HIV escape mutants as in the case of HLA-A-restricted or HLA-B-restricted CTL. 相似文献
35.
Niimi H Mori M Tabata H Minami H Ueno T Hayashi S Kitajima I 《Journal of clinical microbiology》2011,49(9):3316-3320
To achieve the production of a thermostable DNA polymerase free from bacterial DNA contamination, we developed eukaryote-made thermostable DNA (Taq) polymerase. The novel eukaryote-made thermostable DNA polymerase resolves the problem of contaminating bacterial DNA in conventional bacterially made thermostable DNA polymerase as a result of its manufacture and incomplete purification. Using eukaryote-made thermostable DNA polymerase, the sensitive and reliable detection of bacteria becomes feasible for large fields, thereby making the development of a wide range of powerful applications possible. 相似文献
36.
Tsukahara S Momohara S Ikari K Murakoshi K Mochizuki T Kawamura K Kobayashi S Nishimoto K Okamoto H Tomatsu T 《Modern rheumatology / the Japan Rheumatism Association》2007,17(4):344-347
We present two rheumatoid arthritis (RA) patients suffering from disturbances of the symphysis pubis. Radiography revealed
one with pelvic ring disruption with symphysis pubis diastasis, and the other with osteolysis at both pubic rami and disruption
of the superior aspect of the symphysis pubis. Both cases had received long-term corticosteroid therapy, including pulse therapy.
We recommend reducing the corticosteroid dose to prevent disturbances of the symphysis pubis especially in RA patients on
long-term steroid therapy. 相似文献
37.
Asaumi Y Miyanaga T Ito H Sawada K Fujita M Miyazaki M Yagi D Kitamura H Hirano M Maeda K Hayashida Y Ohta K Hayashi H Doden K Hattori M Hashizume Y Kaizaki Y 《Gan to kagaku ryoho. Cancer & chemotherapy》2011,38(8):1325-1328
A 75-year-old man with type 4 advanced gastric cancer was referred to our hospital. We diagnosed the tumor as cStage III B(cT4a, cN2, cM0)gastric cancer. We selected neoadjuvant S-1 combined with CDDP therapy for him. After 2 courses of chemotherapy, the extension of the gastric wall improved. After an additional 2 courses of chemotherapy, the primary tumor revealed a partial response(PR), judged from a barium meal study and upper GI endoscopic findings, and a total gastrectomy with lymph node dissection was performed. The pathological specimens showed no cancer cells in the gastric wall and lymph nodes, so the histological effect was judged as Grade 3. 相似文献
38.
Marushima H Shibata S Asakura T Matsuura T Maehashi H Ishii Y Eda H Aoki K Iida Y Morikawa T Ohkawa K 《International journal of oncology》2011,39(5):1327-1336
In vitro tumor growth in a three-dimensional (3D) architecture has been demonstrated to play an important role in biology not only for developmental organogenesis and carcinogenesis, but also for analyses on reconstitution and maintenance in a variety of biological environments surrounding the cells. In addition to providing architectural similarity to living organisms, 3D culture with a radial flow bioreactor (RFB) can also closely mimic the living hypoxic microenvironment under which specific organogenesis or carcinogenesis occurs. The findings of the present study under the RFB culture conditions show that cancer cells underwent a shift from aerobic to hypoxic energy metabolism, in addition to protein expression to maintain the 3D structure. In RFB-cultured cells, protein stability of hypoxia-inducible factor 1 (HIF1) α, a subunit of HIF1, was increased without upregulation of its mRNA. Under these conditions, PHD2, HIF-prolyl-4-hydroxy-lase 2 and a HIF1 downstream enzyme, were stabilized without affecting the mRNA levels via downregulation of FK506-binding protein 8. PHD2 accumulation, which occurred concomitant with HIF1 stabilization, may have compensated for the lack of oxygen under hypoxic conditions to regulate the HIF levels. 3D-culture-induced overexpression of carbonic anhydrase (another representative HIF downstream enzyme) was found to occur independently of cell density in RFB--cultured cells, suggesting that the RFB provided an adequately hypoxic microenvironment for the cultured cells. From these results, it was hypothesized that the key factors are regulatory molecules, which stabilize and degrade HIF molecules, thereby activating the HIF1 pathway under a hypoxic milieu. 相似文献
39.
40.
J Okuzumi H Nishino M Murakoshi T Yamane Y Kitao M Inagake K Ohya M Yoshida T Takahashi 《Oncology》1992,49(6):492-497
The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly. 相似文献