全文获取类型
收费全文 | 20893篇 |
免费 | 1064篇 |
国内免费 | 151篇 |
专业分类
耳鼻咽喉 | 221篇 |
儿科学 | 447篇 |
妇产科学 | 195篇 |
基础医学 | 2317篇 |
口腔科学 | 376篇 |
临床医学 | 1466篇 |
内科学 | 5878篇 |
皮肤病学 | 435篇 |
神经病学 | 1585篇 |
特种医学 | 792篇 |
外科学 | 3909篇 |
综合类 | 55篇 |
预防医学 | 493篇 |
眼科学 | 403篇 |
药学 | 1113篇 |
1篇 | |
中国医学 | 50篇 |
肿瘤学 | 2372篇 |
出版年
2024年 | 32篇 |
2023年 | 194篇 |
2022年 | 396篇 |
2021年 | 712篇 |
2020年 | 377篇 |
2019年 | 467篇 |
2018年 | 621篇 |
2017年 | 413篇 |
2016年 | 578篇 |
2015年 | 541篇 |
2014年 | 767篇 |
2013年 | 872篇 |
2012年 | 1386篇 |
2011年 | 1618篇 |
2010年 | 897篇 |
2009年 | 800篇 |
2008年 | 1314篇 |
2007年 | 1360篇 |
2006年 | 1321篇 |
2005年 | 1382篇 |
2004年 | 1424篇 |
2003年 | 1279篇 |
2002年 | 1171篇 |
2001年 | 193篇 |
2000年 | 168篇 |
1999年 | 201篇 |
1998年 | 242篇 |
1997年 | 228篇 |
1996年 | 158篇 |
1995年 | 138篇 |
1994年 | 145篇 |
1993年 | 109篇 |
1992年 | 90篇 |
1991年 | 78篇 |
1990年 | 61篇 |
1989年 | 43篇 |
1988年 | 39篇 |
1987年 | 41篇 |
1986年 | 35篇 |
1985年 | 25篇 |
1984年 | 31篇 |
1983年 | 20篇 |
1982年 | 22篇 |
1981年 | 17篇 |
1980年 | 16篇 |
1979年 | 11篇 |
1978年 | 12篇 |
1976年 | 9篇 |
1975年 | 14篇 |
1974年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Yasuyuki Matsushita Yasufumi Kuroda Shinpei Niwa Satoshi Sonehara Chikuma Hamada Isao Yoshimura 《Drug safety》2007,30(8):715-726
BACKGROUND AND OBJECTIVE: Several statistical methods exist for detecting signals of potential adverse drug reactions in spontaneous reporting databases. However, these signal-detection methods were developed using regulatory databases, which contain a far larger number of adverse event reports than the databases maintained by individual pharmaceutical manufacturers. Furthermore, the composition and quality of the spontaneous reporting databases differ between regulatory agencies and pharmaceutical companies. Thus, the signal-detection criteria proposed for regulatory use are considered to be inappropriate for pharmaceutical industry use without modification. The objective of this study was to revise the criteria for signal detection to make them suitable for use by pharmaceutical manufacturers. METHODS: A model comprising 40 drugs and 1000 adverse events was constructed based on a spontaneous reporting database provided by a pharmaceutical company and used in a simulation to investigate appropriate criteria for signal detection. In total, 1000 pseudo datasets were generated with this model, and three statistical methods (proportional reporting ratio [PRR], Bayesian Confidence Propagation Neural Network [BCPNN] and multi-item gamma Poisson shrinker [MGPS]) for signal detection were applied to each dataset. The sensitivity and specificity of each method were evaluated using these pseudo datasets. The optimum critical value for signal detection (i.e. the value that achieved the highest sensitivity with 95% specificity) was identified for each method. The optimum values were also examined with the adverse events classified into two categories according to frequency. The three original detection methods and their revised versions were applied to a real pharmaceutical company database to detect 173 known adverse reactions of four drugs. RESULTS: The 1000 pseudo datasets consisted of an average of 81 862 reports and 11,407 drug-event pairs, including 1192 adverse drug reactions. The sensitivities of PRR, BCPNN and MGPS methods were 49%, 45% and 26%, respectively, whereas their specificities were 95%, 99.6% and 99.99%, respectively; these sensitivities were unacceptably low for pharmaceutical manufacturers, whereas the specificities were acceptable. The highest sensitivity for each method, obtained by changing critical values and maintaining specificity at 95%, was 44%, 62% and 62%, respectively. When adverse events were classified into two categories, sensitivities as high as 75% for regular events and 39% for rare events were achieved with the revised BCPNN method. The critical values of the information component minus two standard deviations (IC - 2SD) index of the revised BCPNN method were greater than -0.7 for regular events and greater than -0.6 for rare events. The revised BCPNN method yielded 51% sensitivity and 89% specificity for the real dataset. CONCLUSION: A lower critical value may be needed when signal-detection methodology is applied to the spontaneous reporting databases of pharmaceutical manufacturers. For example, it is recommended that pharmaceutical manufacturers use the BCPNN method with IC - 2SD criteria of greater than -0.7 for regular events and greater than -0.6 for rare events. 相似文献
992.
Intratumoral estrogens and estrogen receptors in human non-small cell lung carcinoma 总被引:2,自引:0,他引:2
Hiromichi Niikawa Takashi Suzuki Yasuhiro Miki Satoshi Suzuki Shuji Nagasaki Junichi Akahira Seijiro Honma Dean B Evans Shin-Ichi Hayashi Takashi Kondo Hironobu Sasano 《Clinical cancer research》2008,14(14):4417-4426
PURPOSE: The possible involvement of gender-dependent factors has been suggested in human non-small cell lung carcinomas (NSCLC), but their precise roles remain largely unclear. Therefore, we examined intratumoral estradiol concentrations in NSCLC to examine local actions of estrogens in NSCLC. EXPERIMENTAL DESIGN: Fifty-nine frozen specimens of NSCLC were available for liquid chromatography/electrospray tandem mass spectrometry to study intratumoral estradiol concentrations. In addition, A549 NSCLC cells stably expressing estrogen receptor (ER) alpha (A549 + ERalpha) or ERbeta (A549 + ERbeta) were used in vitro studies. RESULTS: Forty-three (73%) of 59 NSCLC showed higher concentration of estradiol in carcinoma tissues than the corresponding nonneoplastic lung tissues from the same patient, and intratumoral estradiol concentrations were significantly (P = 0.0002 and 2.2-fold) higher than the corresponding nonneoplastic lungs. The intratumoral concentration of estradiol was positively correlated with aromatase expression, tumor size, and Ki-67 status in ERalpha- or ERbeta-positive cases. In in vitro studies, estradiol significantly increased cell proliferation of A549 + ERalpha or A549 + ERbeta, which was significantly suppressed by selective ER modulators, tamoxifen or raloxifene. Both A549 + ERalpha and A549 + ERbeta cells expressed aromatase. The cell proliferation level in these cells was significantly increased under treatment with testosterone, and it was inhibited by addition of the aromatase inhibitor letrozole. CONCLUSIONS: These results suggest that estradiol is locally produced in NSCLC mainly by aromatase and plays an important role in the growth of ERalpha- or ERbeta-positive NSCLC. Therefore, use of selective ER modulators and/or aromatase inhibitors may be clinically effective in NSCLC that are positive for both ER and aromatase. 相似文献
993.
Takayoshi Kiba Takashi Inamoto Tsutomu Nishimura Masaya Ueno Kazuhiro Yanagihara Satoshi Teramukai Hironori Kato Masakazu Toi Masanori Fukushima 《BMC cancer》2008,8(1):323
Backgrounds
Prognostic factors are defined as biological or clinical measurement associated with overall survival and/or disease-free survival. Previous studies have shown that patients with estrogen receptor (ER) positive cancers have a better prognosis than patients whose cancers do not have these receptors. 相似文献994.
Lin-Hao Li Li-Jun Wu Yuan-Yuan Jiang Shin-Ichi Tashiro Satoshi Onodera Fumiaki Uchiumi Takashi Ikejima 《Journal of Asian natural products research》2007,9(7):593-602
Silymarin is a polyphenolic flavonoid from milk thistle (Silybum marianum), which has anti-inflammatory, cytoprotective as well as antioxidant effects. Our previous study demonstrated that silymarin has anti-apoptotic effect against UV irradiation. In this study, we assessed the effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells. Pretreatment with silymarin (3 × 10- 4 mol/L) significantly induced cell apoptosis in CH11-treated A375-S2 cells. Mitochondrial transmembrane potential (ΔΨm) was also down-regulated by silymarin pretreatment. Caspase-8, -9, -3 and pan-caspase inhibitors partially reversed silymarin-induced apoptosis of CH11-treated cells. The expression of Fas-associated proteins with death domain (FADD), a downstream molecule of the death receptor pathway, was increased by silymarin pretreatment, followed by cleavage of procaspase-8, whose activation induced cell apoptosis. Moreover, cleavage of procaspase-3 and digestion of its substrate, the inhibitor of caspase-activated DNase (ICAD), were also increased by silymarin pretreatment. These results suggested that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells. 相似文献
995.
Dr. Satoshi Hiraishi Yasunori Horiguchi Nobuyuki Fujino Youtaro Agata Harumi Kawai Masahiro Ohe Kimio Yashiro 《Pediatric cardiology》1991,12(1):6-12
Summary Parasternal two-dimensional and Doppler echocardiography were compared with angiographic, surgical, and postmortem data in 213 patients with various forms of congenital heart disease for its accuracy in determining patency and anatomy of the ductus arteriosus (DA). The age range of the examined patients was from 1 day to 4 years (mean, 7.4 months). Echocardiography was always performed before any invasive procedure. An adequate window for imaging the DA was obtained by parasternal, two-dimensional echocardiography in 209 patients (98%). A persistent ductus arteriosus (PDA) was detected by invasive methods in 79 of 209 patients (38%), and by two-dimensional and Doppler echocardiography in 76 (sensitivity, 96%; specificity, 100%). The echocardiographic and angiographic findings agreed closely as to the duct's morphology. Our technique permits an accurate visualization of the duct in neonates, infants, and small children with various forms of congenital heart disease. 相似文献
996.
Nobuhiro Takeshima M.D. Yoshio Shimizu M.D. Satoshi Umezawa M.D. Yasuo Hirai M.D. Jui-Tung Chen M.D. Ikuno Fujimoto M.D. Kazuhiro Yamauchi M.D. Katsuhiko Hasumi M.D. 《Gynecologic oncology》1994,54(3)
Serum levels of CA125 and CA19-9 were examined in 225 cases with endometrial carcinoma before treatment and 32 cases with recurrent endometrial carcinoma. The positive rates in the 225 cases were 27.1% for CA125, 24.0% for CA19-9, and 38.7% for the combined assay. The serum levels of both CA125 and CA19-9 significantly increased with surgical staging. The presence of lymph node metastasis and extrauterine spread exhibited a marked influence on the serum levels of both CA125 and CA19-9. Myometrial invasion and vessel permeation also increased serum levels of CA125, whereas peritoneal cytology and adnexal metastasis exhibited no influence on CA125 levels or CA19-9 levels. Twenty-five of 33 cases who showed either more than 100 U/ml of CA125 level or more than 100 U/ml of CA19-9 level were classified as surgical stage III or IV. The combined assay demonstrated a 71.9% positive rate at the time of detection of the recurrence (65.6% for CA125, 43.7% for CA19-9). In 34.4% of the 32 recurrent cases, elevated levels of the tumor markers were the first sign of recurrence. These data indicate that the use of CA19-9 in combination with CA125 is noteworthy in the management of patients with endometrial carcinoma. 相似文献
997.
Masayuki Yasuda Satoshi Shiokawa Masaki Yamaguchi Yasuo Suenaga Tetsuya Wada Shiro Nonaka Masashi Nobunaga 《Leukemia & lymphoma》1994,14(3):347-351
We treated a patient with severe aplastic anemia with long-term administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF). When a trilineage response of hematopoiesis was obtained after the first treatment, a chromosomal change [45XX, -7] was observed in 20 of the 20 metaphases examined. Later, we were able to show a monoclonal X inactivation pattern in the phosphoglycerate kinase (PGK) gene in the peripheral blood polymorphonuclear leukocytes and mononuclear cells, indicating the presence of clonal hematopoiesis regardless of the disappearance of the karyotype abnormality. We suggest that it is important to pay close attention to the appearance of clonal hematopoiesis during the administration of G-CSF to patients with idiopathic severe bone marrow aplasia. 相似文献
998.
Hirofumi Nioka Ken-ichi Matsumura Satoshi Nakasu Jyoji Handa 《Journal of neuro-oncology》1994,21(3):233-242
Changes of glycosaminoglycan distribution in and around C6 glioma and ethylnitrosourea(ENU)-induced glioma in rats were investigated using monoclonal antibodies that specifically recognize epitopes on chondroitin-0-sulfate proteoglycan (C-0-S), chondroitin-4-sulfate proteoglycan (C-4-S), dermatan sulfate proteoglycan (DS), chondroitin-6-sulfate proteoglycan (C-6-S) and keratan sulfate proteoglycan (KS) after chondroitinase ABC digestion. In the normal brain tissues, C-0-S was located on the surface of the neurons. In addition, extracellular staining in the cerebral cortex and axoplasmic staining in the brain stem and the reticular thalamic nucleus were seen. C-0-S was negative, however, both in the C6 and ENU-induced gliomas. C-4-S or DS was detected only in some of the neurons in the normal brain tissues. They were detected in the peripheral part of the ENU-induced gliomas, but not in the C6 gliomas. C-6-S was located on the surface of some neurons and in the white matter of the normal brain, but it was not detected in C6 gliomas. In all ENU-induced gliomas, C-6-S was identified in the adventitia of the vascular structures within the tumor. In some of them, C-6-S appeared in the peripheral part of the tumor. KS was immunostained in the glial cells in the hippocampus, corpus callosum, brain stem, and the floor of the third ventricle. It was also detected in the peritumoral brain tissues both in the C6 and ENU-induced rat gliomas. The significance of glycosaminoglycans in these glioma models was discussed. 相似文献
999.
1-{[5'-(3'-methoxy-4'-ethoxycarbonyloxyphenyl)-2',4'-penta-dienoyl]aminoethyl}-4-diphenylmethoxypiperidine(TMK688) is a potent and orally active 5-lipoxygenase inhibitorhaving anti-histamine activity in its moiety. Recently we havefound that TMK688 also inhibits epidermal cyclooxygenase activitywith a potency similar to its inhibiting 5-lipoxygenase. Oraladministration of 30 mg/kg TMK688, a dose which markedly inhibitstumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulatedLTB4 formation in mouse skin, markedly inhibited both TPA-promotedand a non-TPA-type tumor promoter anthralin-promoted skin tumorformation in 7,12-dimethylbenz[a]anthracene (DMBA)-initiatedCD-1 mice. The inhibitory effect of TMK688 was not due to anydamage inflicted on the initiated cells but due to its anti-tumor-promotingactivity. TMK688 not only inhibited two-stage skin carcinogenesisbut also inhibited benzo[a]pyrene-caused complete skin carcinogenesis.Throughout the tumorigenesis experiment, the survival rate ofanimals was 100% and the TMK688-treated mice looked healthy.The body weight gain of TMK688-treated mice was not significantlydifferent from that of non-treated mice. Both TMK688 and 1-{[5'-(3'-methoxy-4'-hydroxyphenyl)-2',4'-pentadienoyl]aminoethyl}-4-diphenylmethoxypiperidine(TMK777), an active metabolite of TMK688 having more potent5-lipoxygenase inhibitory activity and less potent cyclooxygenaseinhibitory activity than TMK688, inhibited epidermal 8-lipoxygenaseactivity induced by a topical application of TPA to mouse skin.The 8-lipoxygenase inhibitory activity of TMK777 was 相似文献
1000.
Significant Increases in Serum CA125 and CA19-9 Following Torsion from an Adenofibroma of the Ovary: A Case Report 总被引:2,自引:0,他引:2
Fujiwara Keiichi; Moriya Takuya; Mikami Yoshiki; Hiratsuka Junichi; Sawada Satoshi; Imajo Yoshinari; Kohno Ichiro 《Japanese journal of clinical oncology》1994,24(2):116-119
Significant increases in the serum levels of cancer antigen125 (CA 125) and carbohydrate antigen 19-9 (CA19-9) were observedover one month prior to the removal of an ovarian adenofibroma.The serum levels of CA125 and CA19-9 decreased rapidly aftersurgery. The surface of the tumor at surgery showed marked inflammation,probably induced by the necrosis produced by torsion. Pathologically,most of the tumor was necrotic, and histo immunochemical stainingof the viable cells was weak for CA125 but intense for CA19-9.Clinicopathological observations of the case suggested thatCA125 and CA19-9 might be stimulated in the cells by inflammationor that originally existing CAT25 and CA19-9 were released fromthe tumor cells following the cell necrosis. 相似文献