全文获取类型
收费全文 | 651篇 |
免费 | 24篇 |
国内免费 | 3篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 33篇 |
妇产科学 | 1篇 |
基础医学 | 44篇 |
口腔科学 | 16篇 |
临床医学 | 68篇 |
内科学 | 141篇 |
皮肤病学 | 70篇 |
神经病学 | 28篇 |
特种医学 | 46篇 |
外科学 | 78篇 |
综合类 | 1篇 |
预防医学 | 8篇 |
眼科学 | 1篇 |
药学 | 101篇 |
中国医学 | 1篇 |
肿瘤学 | 38篇 |
出版年
2023年 | 5篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 6篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 9篇 |
2016年 | 16篇 |
2015年 | 18篇 |
2014年 | 23篇 |
2013年 | 19篇 |
2012年 | 47篇 |
2011年 | 34篇 |
2010年 | 21篇 |
2009年 | 20篇 |
2008年 | 41篇 |
2007年 | 38篇 |
2006年 | 38篇 |
2005年 | 47篇 |
2004年 | 35篇 |
2003年 | 50篇 |
2002年 | 32篇 |
2001年 | 15篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 5篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 6篇 |
1988年 | 4篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 3篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
1970年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有678条查询结果,搜索用时 14 毫秒
121.
Suzuki N Suzuki T Inagaki K Ito S Kono M Fukai K Takama H Sato K Ishikawa O Abe M Shimizu H Kawai M Horikawa T Yoshida K Matsumoto K Terui T Tsujioka K Tomita Y 《The Journal of investigative dermatology》2005,124(6):1186-1192
Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant inheritance. We have clarified for the first time four pathological mutations of the double-stranded RNA-specific adenosine deaminase gene (ADAR1 or DSRAD) in four DSH pedigrees. In this paper, we report 16 novel mutations containing six missense substitutions (p.V906F, p.K1003R, p.G1007R, p.C1036S, p.S1064F, p.R1078C), two splice site mutations (IVS2+2T>G, IVS8+2T>A), six frameshift mutations (p.H216fs, p.K433fs, p.G507fs, p.P727fs, p.V955fs, p.K1201fs), and two nonsense mutations (p.R426X, p.Q600X) found in Japanese patients with DSH. We did not establish any clear correlation between the clinical phenotypes and the genotypes of ADAR1 gene mutations in our examination of 16 cases plus four pedigrees. None of the different mutations identified in our studies of 20 cases suggested any founder effect. Furthermore, we did not identify any mutations in the ADAR1 gene of three patients with dyschromatosis universalis hereditaria or three patients with acropigmentatio reticularis, indicating that the two diseases are completely different from DSH, although they have sometimes been suggested to be phenotypical variations of DSH. 相似文献
122.
Hayashi Y Matsuda R Maitani T Ito K Nishimura W Imai K Maeda M 《Journal of pharmaceutical and biomedical analysis》2004,36(1):225-229
This paper puts forward a method to describe an equation of the within-plate uncertainty (relative standard deviation (R.S.D.) of measurements) as a function of analyte concentration in sandwich enzyme-linked immunosorbent assay (ELISA). A kit for thyroid stimulating hormone is taken as an example. The pipetting procedures of analyte solution and chromogen-substrate solution and absorbance inherent to the wells of a microplate are identified as major error sources and their variability is included as parameters in the uncertainty equation. These parameters can be determined by the experiments with distilled water. The theoretical R.S.D. is shown to be in good agreement with the results of the repeated experiments using the real samples. Since the theory gives a continuous plot of R.S.D. against concentration, the uncertainty structure of the ELISA kit can be recognized over a wide concentration range and the detection limit and quantitation range can easily be determined on the plot. 相似文献
123.
Kunoh T Noda T Koseki K Sekigawa M Takagi M Shin-ya K Goshima N Iemura S Natsume T Wada S Mukai Y Ohta S Sasaki R Mizukami T 《Molecular cancer therapeutics》2010,9(11):2934-2942
There are several human genes that may encode proteins whose functions remain unknown. To find clues to their functions, we used the mutant yeast defective in Mad2, a component of the spindle checkpoint complex. Phenotypes that were provoked by the expression of a human C18orf26 protein in the mutant yeast encouraged further characterization of this protein in human cells. This protein was designated dynAP (dynactin-associated protein) because of its interaction with dynactin subunits that comprised a microtubule-based motor protein complex. The dynAP is a transmembrane protein localizing to Golgi apparatus and plasma membrane in a microtubule-dependent manner. This protein was expressed in half of human cancer cell lines but barely in normal human fibroblasts tested. The SV40-transformed fibroblasts expressed dynAP. Importantly, the expression of dynAP activated Akt (also known as protein kinase B) by promoting Ser??3 phosphorylation required for the full activation, whereas knockdown of dynAP abolished this activation. The ergosterol-related compounds identified by the yeast cell-based high-throughput screen abrogated activation of Akt and induced apoptosis in a dynAP-dependent manner. We propose a possible advantage of dynAP expression in cancer cells; the survival of cancer cells that express dynAP is supported by dynAP-induced activation of Akt, sustaining high rates of proliferation. The inactivation of dynAP by the selected compounds nullifies this advantage, and thereby, the apoptotic machinery is allowed to operate. Taken together, dynAP can be a new target for cancer therapy, and the selected chemicals are useful for developing a new class of anticancer drugs. 相似文献
124.
125.
Takane H Kawamoto K Sasaki T Moriki K Moriki K Kitano H Higuchi S Otsubo K Ieiri I 《Cancer chemotherapy and pharmacology》2009,63(6):1165-1169
Introduction To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes.
Case report A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m2) on days 1, 8 and 15 in combination with docetaxel (60 mg/m2) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile
grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38
was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs.
Conclusion The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic
or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities. 相似文献
126.
Nishihara H Ozaki Y Ito T Yoshinaga T Tabu K Tanino M Nagashima K Tanaka S 《Brain tumor pathology》2008,25(1):45-49
Central nervous system (CNS) neuroblastoma/ganglioneuroblastoma is one of the embryonal tumors with neuronal differentiation
found in young adults, but it is most common in children, especially in those below the age of 5 years, whereas extraventricular
neurocytoma, a rare neuroepithelial tumor with neuronal differentiation, mostly affects young adults. Here we present a rare
case of cerebral ganglioneuronal tumor that occurred in a 32-year-old woman. The patient suffered from tonic convulsion, and
computed tomography demonstrated a well-demarcated, round tumor 3.3 cm in size with marked calcification in the right parietal
lobe. Histological analysis revealed diffuse infiltration of small, round cells with scattered large ganglion-like cells.
Immunohistochemically, the tumor cells did not react with any neuronal molecules, except for chromogranin A in ganglion-like
large tumor cells, but electron microscopy demonstrated the presence of synapse-like nerve terminal structures without mature
postsynaptic density, suggesting the presence of neoplastic tumor components with neuronal differentiation; thus, this tumor
was diagnosed as CNS ganglioneuroblastoma with possible low-grade malignancy because the Mib-1 labeling index was less than
3%–4%. Here we discuss the histological entity of cerebral ganglioneuronal tumors, including extraventricular neurocytoma. 相似文献
127.
128.
129.
Kinoshita Y Tajiri T Ieiri S Nagata K Taguchi T Suita S Yamazaki K Yoshino I Maehara Y Kohashi K Yamamoto H Oda Y Tsuneyoshi M 《Pediatric surgery international》2007,23(6):595-599
We herein describe a 4-year-old boy who after being treated for pneumonia showed an abnormal shadow at the hilus of the right
lung on chest X-rays with continued inflammatory findings in his laboratory data. CT and MR investigations suggested the existence
of a neoplasm at that site. An open biopsy was thus performed for a definite diagnosis. The histological findings and the
expression of TPM3–ALK fusion gene confirmed a diagnosis of an inflammatory myofibroblastic tumor. A right upper and middle
lobectomy including the tumor was thus performed for a complete resection. In addition to the histological diagnosis, the
detection of the tumor specific fusion gene provided objective evidence in making a diagnosis. 相似文献
130.
5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients 总被引:2,自引:0,他引:2 下载免费PDF全文
Takahashi H Ieiri I Wilkinson GR Mayo G Kashima T Kimura S Otsubo K Echizen H 《Blood》2004,103(8):3055-3057
White and Japanese patients require different warfarin dosages to achieve therapeutic anticoagulation, but this can be only partly explained by genetic variability in the coding region of CYP2C9-a critical enzyme in the drug's metabolism. Accordingly, analysis of the -2.1-kb 5'-flanking region of CYP2C9 was undertaken in 22 white and 38 Japanese patients whose unbound oral clearance of S-warfarin had been previously determined. Thirteen single nucleotide polymorphisms (SNPs) were identified, some of which were in linkage disequilibrium with functionally defective coding region variants. Those 5'-flanking patterns linked with at least one CYP2C9*3 allele or CYP2C9*2/*3 were associated with reduced CYP2C9 activity and warfarin dose. Japanese patients possessing the wild-type promoter and coding sequences had significantly (P <.01) greater CYP2C9 activity than white patients with the corresponding genotype. In conclusion, either unidentified polymorphisms further upstream in the promoter region or environmental factor(s) account for the differences in the warfarin doses between whites and Japanese. 相似文献