全文获取类型
收费全文 | 703篇 |
免费 | 35篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 12篇 |
妇产科学 | 22篇 |
基础医学 | 116篇 |
口腔科学 | 24篇 |
临床医学 | 45篇 |
内科学 | 150篇 |
皮肤病学 | 8篇 |
神经病学 | 102篇 |
特种医学 | 24篇 |
外科学 | 58篇 |
综合类 | 3篇 |
预防医学 | 14篇 |
眼科学 | 3篇 |
药学 | 20篇 |
肿瘤学 | 132篇 |
出版年
2023年 | 8篇 |
2021年 | 15篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 12篇 |
2016年 | 14篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 14篇 |
2012年 | 21篇 |
2011年 | 26篇 |
2010年 | 21篇 |
2009年 | 18篇 |
2008年 | 29篇 |
2007年 | 28篇 |
2006年 | 35篇 |
2005年 | 37篇 |
2004年 | 53篇 |
2003年 | 48篇 |
2002年 | 37篇 |
2001年 | 31篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 16篇 |
1997年 | 13篇 |
1996年 | 11篇 |
1995年 | 12篇 |
1994年 | 19篇 |
1993年 | 11篇 |
1992年 | 18篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 17篇 |
1988年 | 12篇 |
1987年 | 17篇 |
1986年 | 5篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有739条查询结果,搜索用时 968 毫秒
1.
Summary Histological, ultrastructural and morphometrical observations on Clarke's column were carried out in 18 patients with sporadic amyotrophic lateral sclerosis (ALS) and 15 age-matched control subjects. Of the 18 ALS patients 6 had been on a respirator before death. Bunina bodies were found in the neuronal cytoplasm in 7 of the 12 non-respirator-supported ALS patients and in 3 of the 6 respirator-supported patients. The number of spheroids was significantly higher in the non-respirator-supported patients (P<0.01) than in the control subjects; however, the number in the respirator-supported patients was about equal to that in the controls. The number of neurons in Clarke's column in the non-respirator-supported ALS patients was not reduced, but in the respirator-supported patients they tended to disappear with time after respiratory support. These findings suggest that Clarke's column neurons are also involved primarily in the disease process in sporadic ALS. However, they may begin to disappear only after the patients require respiratory support.Supported in part by a research grant for CNS degenerative diseases from the Ministry of Health and Welfare, Japan 相似文献
2.
3.
Noriyuki Kimura Toshihide Kumamoto Hidetsugu Ueyama Hideo Horinouchi Eisaku Ohama 《Neuropathology》2007,27(6):522-530
We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum‐treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum‐treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum‐treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non‐phosphorylated high molecular weight neurofilament (neurofilament‐H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament‐H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum‐treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum‐treated rabbits. 相似文献
4.
This report describes an experimental model of chronic tonsillar herniation and its effects on the spinal cord. In ten rats, a small piece of chemically induced mammary cancer was transplanted to the supraoccipital bone. In all cases, the transplanted cancers grew into the posterior fossa, destroying the supraoccipital bone and compressing the cerebellum extradurally. In six of the ten rats, tonsillar herniation was observed at 8–14 weeks after transplantation. Transdural infiltration of the tumor cells was not apparent in any animal. In those rats with tonsillar herniation (n=6), the spinal cord from the C5 to the T8 segments showed enlargement of the central canal without exception. Histological examination revealed the following changes: stretching and thinning of the ependymal cells; swelling of the astrocytic processes; and extracellular edema, predominantly in the dorsal gray matter, but also in the ventral inner portion of the dorsal column. In the control group (n=4) and those rats without tonsillar herniation (n=4), such histological changes of the spinal cord were not observed. Although the lesions can not be regarded as representing mature syringomyelia, they most likely constitute an earlier evolutionary stage. 相似文献
5.
Tetsuya Yamamoto Kazunori Yoneda Eisaku Ueta Yukihiro Tatemoto Tokio Osaki 《International journal of clinical oncology / Japan Society of Clinical Oncology》1996,1(3):150-156
Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral
squamous cell carcinoma.
Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and60Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×108 cells) and small doses of interleukin-2(≈3×105 U) and interferon-gamma (≈2×105U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group].
Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively;
and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated
with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the
tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the
CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal
increase of LeY-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative
tumors in the CRI(+) group.
Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer
effects resulting from necrosis and apoptosis. 相似文献
6.
Shohachi Suzuki Satoshi Nakamura Hideki Ishida Takanori Sakaguchi Atsushi Serizawa Hiroyuki Konno Shozo Baba Hiroyuki Muro Isao Kosugi Eisaku Gu 《Surgery today》1996,26(8):635-639
Hepatic angiomyolipoma is a rare tumor composed of spindle-shaped and epithelioid smooth muscle cells, adipose tissue, and proliferating blood vessels. We report the first documented case of this tumor developing in a patient with ulcerative colitis. A solitary tumor (7.5×7.5×7cm) was detected in the left lateral segment of the liver and a left hepatic lobectomy was performed. The diagnosis of angiomyolipoma was confirmed by a pathological examination. We also review the literature on previously reported cases of hepatic angiomyolipoma. 相似文献
7.
Regulation of Fungal Infection by a Combination of Amphotericin B and Peptide 2, a Lactoferrin Peptide That Activates Neutrophils 下载免费PDF全文
Tetsuro Okamoto Toyohiro Tanida Benjuan Wei Eisaku Ueta Tetsuya Yamamoto Tokio Osaki 《Clinical and Vaccine Immunology : CVI》2004,11(6):1111-1119
To establish a novel strategy for the control of fungal infection, we examined the antifungal and neutrophil-activating activities of antimicrobial peptides. The duration of survival of 50% of mice injected with a lethal dose of Candida albicans (5 × 108 cells) or Aspergillus fumigatus (1 × 108 cells) was prolonged 3 to 5 days by the injection of 10 μg of peptide 2 (a lactoferrin peptide) and 10 μg of α-defensin 1 for five consecutive days and was prolonged 5 to 13 days by the injection of 0.1 μg of granulocyte-monocyte colony-stimulating factor (GM-CSF) and 0.5 μg of amphotericin B. When mice received a combined injection of peptide 2 (10 μg/day) with amphotericin B (0.5 μg/day) for 5 days after the lethal fungal inoculation, their survival was greatly prolonged and some mice continued to live for more than 5 weeks, although the effective doses of peptide 2 for 50 and 100% suppression of Candida or Aspergillus colony formation were about one-third and one-half those of amphotericin B, respectively. In vitro, peptide 2 as well as GM-CSF increased the Candida and Aspergillus killing activities of neutrophils, but peptides such as α-defensin 1, β-defensin 2, and histatin 5 did not upregulate the killing activity. GM-CSF together with peptide 2 but not other peptides enhanced the production of superoxide (O2−) by neutrophils. The upregulation by peptide 2 was confirmed by the activation of the O2−-generating pathway, i.e., activation of large-molecule guanine binding protein, phosphatidyl-inositol 3-kinase, protein kinase C, and p47phox as well as p67phox. In conclusion, different from natural antimicrobial peptides, peptide 2 has a potent neutrophil-activating effect which could be advantageous for its clinical use in combination with antifungal drugs. 相似文献
8.
Yuji Okuyama Mitsuhiko Yamada Chikako Kondo Eisaku Satoh Shojiro Isomoto Takashi Shindo Yoshiyuki Horio Masafumi Kitakaze Masatsugu Hori Y. Kurachi 《Pflügers Archiv : European journal of physiology》1998,435(5):595-603
The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel
was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents
were inhibited by glibenclamide with a K
i value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited
by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+
i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+
i. Uridine 5’-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing
ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate
the molecular mechanisms characterizing the KATP channel.
Received: 24 October 1997 / Received after revision and accepted: 4 December 1997 相似文献
9.
Jin GS Kondo E Miyake T Shibata M Takashima T Liu YX Hayashi K Akagi T Yoshino T 《Acta medica Okayama》2004,58(4):197-205
FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast. 相似文献
10.
Tanaka Y Kato K Notohara K Nakatani Y Miyake T Ijiri R Nishimata S Ishida Y Kigasawa H Ohama Y Tsukayama C Kobayashi Y Horie H 《The Journal of pathology》2003,199(2):185-190
This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL. 相似文献