全文获取类型
收费全文 | 674篇 |
免费 | 36篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 9篇 |
妇产科学 | 5篇 |
基础医学 | 163篇 |
口腔科学 | 21篇 |
临床医学 | 48篇 |
内科学 | 124篇 |
皮肤病学 | 30篇 |
神经病学 | 35篇 |
特种医学 | 37篇 |
外科学 | 76篇 |
综合类 | 6篇 |
预防医学 | 23篇 |
眼科学 | 6篇 |
药学 | 24篇 |
中国医学 | 2篇 |
肿瘤学 | 93篇 |
出版年
2023年 | 7篇 |
2022年 | 11篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 21篇 |
2018年 | 12篇 |
2017年 | 12篇 |
2016年 | 21篇 |
2015年 | 10篇 |
2014年 | 16篇 |
2013年 | 18篇 |
2012年 | 36篇 |
2011年 | 40篇 |
2010年 | 21篇 |
2009年 | 20篇 |
2008年 | 27篇 |
2007年 | 38篇 |
2006年 | 35篇 |
2005年 | 31篇 |
2004年 | 27篇 |
2003年 | 32篇 |
2002年 | 30篇 |
2001年 | 11篇 |
2000年 | 19篇 |
1999年 | 25篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 14篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有710条查询结果,搜索用时 15 毫秒
1.
Kunihiko Sasai Takashi Adachi Kouki Togano Ei Wakabayashi Hiroyuki Ohnari Hirokazu Iida 《The spine journal》2006,6(4):464-467
BACKGROUND CONTEXT: There is no report in the literature of two-level disc herniation in the cervical and thoracic spine presenting with spastic paresis/paralysis exclusively in the bilateral lower extremities. PURPOSE: To identify the clinical characteristics of specific myelopathy resulting from C6-C7 disc herniation through a case with spastic paresis in the lower extremities without upper extremities symptoms due to separate disc herniation in the cervical and thoracic spine, which was surgically removed in two stages. STUDY DESIGN/SETTING: A case report. METHODS: A 48-year-old man developed a gait disturbance as well as weakness and numbness in the lower extremities. Thoracic magnetic resonance imaging (MRI) showed a T11-T12 disc herniation, which was removed under the surgical microscope through a minimally invasive posterior approach. He improved, but 2 months after surgery developed recurrent numbness and spasticity. On this occasion, no evidence of recurrence of the thoracic disc herniation could be identified, but cervical MRI demonstrated a compressed spinal cord at the C6-C7 level. The patient had no neurological findings in the upper extremities. The herniated disc at C6-C7 was removed under the surgical microscope with laminoplasty. RESULTS: The symptoms gradually improved after surgery. At the present time, 2 years and 9 months after the initial operation, the patient had a stable gait and was able to work. CONCLUSIONS: Our experience suggests that in the diagnosis of patients with spastic paresis and sensory disturbances in the lower extremities, spinal cord compression should be explored by imaging studies not only in the thoracic spine but also in the cervical spine, especially at the C6-C7 level, even if the symptoms and abnormal neurological findings are absent in the upper extremities. 相似文献
2.
Our previous study showed that the saliency of a target increases the gain of smooth pursuit initiation. In this study, we examined the interocular transfer of this effect in five humans. A square red frame surrounding the target was used as a cue to indicate the initial target position. In the cue condition, the responses were similar, irrespective of the eye to which the cue was presented, and were significantly larger than in the no-cue condition. The result suggests that central pathways that receive input from both eyes mediate the effect of saliency on smooth pursuit initiation. 相似文献
3.
Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts 总被引:18,自引:0,他引:18 下载免费PDF全文
Inai T Mancuso M Hashizume H Baffert F Haskell A Baluk P Hu-Lowe DD Shalinsky DR Thurston G Yancopoulos GD McDonald DM 《The American journal of pathology》2004,165(1):35-52
Angiogenesis inhibitors are receiving increased attention as cancer therapeutics, but little is known of the cellular effects of these inhibitors on tumor vessels. We sought to determine whether two agents, AG013736 and VEGF-Trap, that inhibit vascular endothelial growth factor (VEGF) signaling, merely stop angiogenesis or cause regression of existing tumor vessels. Here, we report that treatment with these inhibitors caused robust and early changes in endothelial cells, pericytes, and basement membrane of vessels in spontaneous islet-cell tumors of RIP-Tag2 transgenic mice and in subcutaneously implanted Lewis lung carcinomas. Strikingly, within 24 hours, endothelial fenestrations in RIP-Tag2 tumors disappeared, vascular sprouting was suppressed, and patency and blood flow ceased in some vessels. By 7 days, vascular density decreased more than 70%, and VEGFR-2 and VEGFR-3 expression was reduced in surviving endothelial cells. Vessels in Lewis lung tumors, which lacked endothelial fenestrations, showed less regression. In both tumors, pericytes did not degenerate to the same extent as endothelial cells, and those on surviving tumor vessels acquired a more normal phenotype. Vascular basement membrane persisted after endothelial cells degenerated, providing a ghost-like record of pretreatment vessel number and location and a potential scaffold for vessel regrowth. The potent anti-vascular action observed is evidence that VEGF signaling inhibitors do more than stop angiogenesis. Early loss of endothelial fenestrations in RIP-Tag2 tumors is a clue that vessel phenotype may be predictive of exceptional sensitivity to these inhibitors. 相似文献
4.
Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene. 相似文献
5.
Yamasaki M Takeshima Y Fujii S Kitaguchi S Matsuura M Tagawa K Inai K 《Pathology international》2000,50(10):778-785
Bronchiolo-alveolar carcinoma (BAC) is a type of lung adenocarcinoma characterized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non-sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (AAH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction-SSCP analysis and direct sequencing to examine a point mutation of the p53 gene at exons 5-8. At the TP53 locus, the frequencies of LOH showed a statistical rank-difference correlation among AAH, NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differences of LOH among AAH, NSBAC and SBAC. We detected a significant statistical rank-difference correlation in the p53 mutation among AAH, NSBAC and SBAC. These findings suggest that a process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and LOH of 3p and 9p might be an early event of carcinogenesis, while the p53 mutation might be a later event. 相似文献
6.
Acidic mucopolysaccharides enhanced C1INA activity against C1s. The presence of heparin in the reaction mixture of C1INA and C1s markedly enhanced the inactivation of C1s by potentiating C1INA activity. Treatment of serum with C1s resulted in the inactivation of C4 hemolytic activity, but this inactivation of C4 by C1s was prevented by the presence of heparin presumably due to the enhancement of C1INA activity normally present in serum. The other acidic mucopolysaccharides, chondroitin sulfates A, B and C, were also effective on potentiating C1INA activity against C1s, but they were less active than heparin. The enhancement of C1INA activity by heparin was not observed in the reaction between C1INA and plasmin. 相似文献
7.
K Nagaki K Iida M Okubo S Inai 《International archives of allergy and applied immunology》1978,57(3):221-232
The reaction mechanisms of beta1H were studied. The generation of alternative pathway C3 and C5 convertases on the cell surface as well as in the fluid phase was inhibited by beta1H globulin. The cell preparation bearing the C3b site could bind beta1H with little effect on the C3b hemolytic activity. Bound beta1H was dissociated by the action of C3bINA and C3bINA-treated C3b bearing cell did not bind beta1H anymore. Cell-bound beta1H was also dissociated by the action of B (or Bb). From these and other results, the following conclusions were obtained. The C3b site-bearing cell could bind beta1H on the C3c region of C3b molecules facilitating the C3bINA action on C3b, and beta1H shared the same binding site with B (or Bb) inhibiting the generation of the alternative pathway convertases competitively. 相似文献
8.
Tetsuichiro Inai Akihito Sengoku Eiji Hirose Hiroshi Iida Yosaburo Shibata 《Anatomical record (Hoboken, N.J. : 2007)》2007,290(11):1431-1438
Claudins are integral membrane proteins at tight junctions (TJs) and form TJ strands. In the present study, we found that claudin‐7 was localized along the entire lateral membranes of epididymal epithelium, including the apical junctional region throughout the epididymis, but claudin‐8 was restricted to the apical junctional region. This finding raises the possibility that aberrant TJ strands may be formed on lateral membranes. Thus, we focused on examining whether TJ strands exist on lateral membranes of epididymal epithelium. Freeze‐fracture electron microscopy showed that aberrant TJ strands were observed in only a few principal cells in all segments of the epididymis except for the initial segment, indicating that the occurrence of aberrant strands is very rare. Aberrant TJ strands were smooth and not subdivided into individual particles in the protoplasmic face, and complementary grooves in the extracellular face were almost free of particles. Aberrant TJ strands in the distal caput and corpus epididymis were accompanied by many vesicle‐like structures but those in the proximal caput and cauda epididymis were not. These results suggest that most of claudin‐7 in lateral membranes may exist in a nonpolymerized form and may play some different roles other than the formation of TJ strands, for example, in the formation of a pool of claudin proteins or in the reinforcement of cell adhesion. Anat Rec, 1431‐1438, 2007. © 2007 Wiley‐Liss, Inc. 相似文献
9.
Experimental autoimmune thyroiditis in nonobese diabetic mice lacking interferon regulatory factor-1
Jin Z Mori K Fujimori K Hoshikawa S Tani J Satoh J Ito S Satomi S Yoshida K 《Clinical immunology (Orlando, Fla.)》2004,113(2):187-192
Interferon regulatory factor-1 (IRF-1) is pivotal in the regulation of interferon (IFN)-mediated immune reactions, and studies suggest that IRF-1 is involved in the development of autoimmune diseases. IRF-1+/+, +/-, and -/- nonobese diabetic (NOD) mice were immunized with mouse thyroglobulin (mTg) to determine whether IRF-1 is required in experimental autoimmune thyroiditis (EAT), a murine model for Hashimoto's thyroiditis (HT). IRF-1-deficient mice developed EAT and anti-mTg antibodies comparable to IRF-1+/+ and +/- mice. Whereas both CD4+ and CD8+ T cells were found in thyroids of IRF-1+/+ mice, the latter was not in IRF-1-/- mice. Major histocompatibility complex class II antigen was comparably expressed in thyroids of IRF-1+/+ and -/- mice. Lack of IRF-1 resulted in decreased CD8+ T cell number in the spleen and reduced IFNgamma production by splenocytes. Our results suggest that IRF-1 is not pivotal in EAT in NOD mice. 相似文献
10.
Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung 总被引:4,自引:0,他引:4
Awaya H Takeshima Y Amatya VJ Furonaka O Tagawa K Kohno N Inai K 《Pathology international》2004,54(7):486-489
We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung. 相似文献