全文获取类型
收费全文 | 888篇 |
免费 | 55篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 25篇 |
妇产科学 | 9篇 |
基础医学 | 141篇 |
口腔科学 | 32篇 |
临床医学 | 72篇 |
内科学 | 175篇 |
皮肤病学 | 9篇 |
神经病学 | 138篇 |
特种医学 | 22篇 |
外科学 | 90篇 |
综合类 | 3篇 |
预防医学 | 24篇 |
眼科学 | 39篇 |
药学 | 42篇 |
肿瘤学 | 117篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 11篇 |
2018年 | 15篇 |
2017年 | 16篇 |
2016年 | 19篇 |
2015年 | 16篇 |
2014年 | 20篇 |
2013年 | 20篇 |
2012年 | 43篇 |
2011年 | 46篇 |
2010年 | 39篇 |
2009年 | 27篇 |
2008年 | 48篇 |
2007年 | 47篇 |
2006年 | 46篇 |
2005年 | 51篇 |
2004年 | 62篇 |
2003年 | 53篇 |
2002年 | 43篇 |
2001年 | 35篇 |
2000年 | 29篇 |
1999年 | 24篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 10篇 |
1995年 | 15篇 |
1994年 | 22篇 |
1993年 | 15篇 |
1992年 | 8篇 |
1991年 | 12篇 |
1990年 | 12篇 |
1989年 | 10篇 |
1988年 | 9篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1983年 | 7篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有944条查询结果,搜索用时 93 毫秒
1.
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
2.
A 42-year-old woman with progressive myelopathy and mononeuritis multiplex is reported. The neurological examination on admission revealed hyperreflexia of the four extremities with pathological reflexes and moderate muscle weakness of the lower extremities with spasticity. Sensory disturbance was distributed on the areas of the bilateral lateral cutaneous femoral, the superficial peroneal and sural nerves. The antibody to HTLV-I in the serum and cerebrospinal fluid was more than 8192X and 512X, respectively. No sensory potential was recorded in the sensory conduction study of bilateral lateral femoral cutaneous nerves. Corticosteroid therapy caused a marked improvement of the sensory and urinary disturbances and had a slight effect on the spastic gait. Our nerve conduction study found small sensory potentials with normal conduction velocities in the bilateral lateral femoral cutaneous nerves. These results suggested the presence of an axonal degeneration in the peripheral nerves in this case. There have been no reports in the literature regarding a case of HAM with mononeuritis multiplex. 相似文献
3.
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
4.
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
5.
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
![点击此处可从《Clinical and Vaccine Immunology : CVI》网站下载免费的PDF全文](/ch/ext_images/free.gif)
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
6.
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
7.
Increase of gamma/delta T cells in hospital workers who are in close contact with tuberculosis patients. 总被引:4,自引:1,他引:4
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
C Ueta I Tsuyuguchi H Kawasumi T Takashima H Toba S Kishimoto 《Infection and immunity》1994,62(12):5434-5441
gamma/delta T cells are likely to participate in the immune response to tuberculous infection in humans. In this study, we carried out an investigation to characterize the responsiveness of gamma/delta T cells from tuberculous patients and healthy individuals to mycobacterial stimulation in vitro. Healthy subjects were assigned to the following two groups: those who had been exposed to tuberculosis (contacts) and those who had not been exposed (noncontacts). The percent gamma/delta T cells in fresh peripheral blood obtained from health care workers who were tuberculin skin test positive and who had constant contact with patients with active tuberculosis (healthy contacts) was significantly higher, whereas healthy noncontacts showed the normal range of gamma/delta T cells. Patients with active pulmonary tuberculosis also had low levels of gamma/delta T cells. HLA-DR antigen-bearing activated gamma/delta T cells were observed in higher percentages among healthy contacts than among healthy noncontacts or patients with pulmonary tuberculosis. In healthy contacts, gamma/delta T cells increased as a percentage of peripheral blood mononuclear cells after in vitro stimulation with purified protein derivative (PPD) tuberculin compared with the percentage of fresh peripheral blood mononuclear cells that they made up, whereas no such increase was observed in patients with tuberculosis or in healthy noncontacts. Phenotypic analysis of the gamma/delta T cells in healthy contacts, which increased in number in vitro in response to PPD, revealed the preferential outgrowth of CD4+ V gamma 2+ gamma/delta T cells. This expansion of gamma/delta T cells by PPD required accessory cells, and it was inhibited by the addition of an antibody against HLA-DR in culture. Proteolytic digestion of PPD showed that gamma/delta T cells increased in number in response to peptide, but not nonpeptide, components of PPD. These findings suggest that gamma/delta T cells, especially CD4+ V gamma 2+ gamma/delta T cells, may participate in the immune surveillance of tuberculous infections in humans. 相似文献
8.
Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy. 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells. 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.
Tachibana H Matsumoto N Cheng XJ Tsukamoto H Yoshihara E 《Clinical and diagnostic laboratory immunology》2004,11(6):1085-1088
We previously produced, in Escherichia coli, a human monoclonal antibody Fab fragment, CP33, specific for the galactose- and N-acetyl-D-galactosamine-inhibitable lectin of Entamoeba histolytica. To prepare antibodies with a higher affinity to the lectin, recombination PCR was used to exchange Ser91 and Arg96 in the third complementarity-determining region of the light chain with other amino acids. The screening of 200 clones of each exchange by an indirect fluorescent antibody test showed that 14 clones for Ser91 and nine clones for Arg96 reacted strongly with E. histolytica trophozoites. Sequence analyses revealed that the substituted amino acids at Ser91 were Ala in five clones, Gly in three clones, Pro in two clones, and Val in two clones, while the amino acid at position 96 was substituted with Leu in three clones. The remaining eight clones exhibited no amino acid change at position 91 or 96. These mutant Fab fragments were purified and subjected to a surface plasmon resonance assay to measure the affinity of these proteins to the cysteine-rich domain of lectin. Pro or Gly substitution for Ser91 caused an increased affinity of the Fab, but substitution with Ala or Val did not. The replacement of Arg96 with Leu did not affect affinity. These results demonstrate that modification of antibody genes by recombination PCR is a useful method for affinity maturation and that amino acid substitution at position 91 yields Fabs with increased affinity for the lectin. 相似文献