全文获取类型
收费全文 | 9124篇 |
免费 | 432篇 |
国内免费 | 87篇 |
专业分类
耳鼻咽喉 | 81篇 |
儿科学 | 160篇 |
妇产科学 | 72篇 |
基础医学 | 1004篇 |
口腔科学 | 124篇 |
临床医学 | 467篇 |
内科学 | 2675篇 |
皮肤病学 | 144篇 |
神经病学 | 664篇 |
特种医学 | 372篇 |
外科学 | 1719篇 |
综合类 | 41篇 |
预防医学 | 219篇 |
眼科学 | 169篇 |
药学 | 552篇 |
中国医学 | 13篇 |
肿瘤学 | 1167篇 |
出版年
2024年 | 14篇 |
2023年 | 68篇 |
2022年 | 126篇 |
2021年 | 250篇 |
2020年 | 130篇 |
2019年 | 175篇 |
2018年 | 220篇 |
2017年 | 189篇 |
2016年 | 233篇 |
2015年 | 249篇 |
2014年 | 315篇 |
2013年 | 368篇 |
2012年 | 603篇 |
2011年 | 624篇 |
2010年 | 339篇 |
2009年 | 354篇 |
2008年 | 610篇 |
2007年 | 656篇 |
2006年 | 640篇 |
2005年 | 632篇 |
2004年 | 602篇 |
2003年 | 568篇 |
2002年 | 561篇 |
2001年 | 94篇 |
2000年 | 78篇 |
1999年 | 105篇 |
1998年 | 137篇 |
1997年 | 94篇 |
1996年 | 80篇 |
1995年 | 84篇 |
1994年 | 65篇 |
1993年 | 46篇 |
1992年 | 53篇 |
1991年 | 44篇 |
1990年 | 35篇 |
1989年 | 30篇 |
1988年 | 21篇 |
1987年 | 20篇 |
1986年 | 11篇 |
1985年 | 10篇 |
1984年 | 13篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有9643条查询结果,搜索用时 0 毫秒
101.
Takahiro Zenda MD Takaharu Masunaga Bungo Fuwa Toshihide Okada Yasuo Ontachi Yukio Kondo Shinji Nakao Hiroshi Minato 《Journal of gastrointestinal cancer》2005,36(2):113-119
A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas. 相似文献
102.
103.
104.
Shinji Yamamoto Yoko Yoshida Masaru Aoyagi Kikuo Ohno Kimiyoshi Hirakawa Hirofumi Hamada 《Clinical cancer research》2002,8(3):913-921
PURPOSE: Recombinant adenoviral vectors are widely used in clinical and experimental studies to treat malignant tumors. Recently, host immune responses have been proposed as a major limitation in using adenoviral vectors for repeated gene delivery. We demonstrate another limitation unrelated to host immunity. EXPERIMENTAL DESIGN: We repeatedly transduced an adenoviral vector expressing the human p53 gene (AxCIhp53) into U373MG, a p53-susceptible cell line, and established the AxCIhp53-resistant cell line U373R. Most U373R cells survived even after AxCIhp53 treatment due to reduced transduction efficiency. Expression levels of adenovirus receptors were estimated to investigate the cause of reduced transduction efficiency. The mutant vector was used to overcome the resistance. RESULTS: The transduction efficiency of an adenoviral vector possessing the reporter LacZ gene (AxCAZ2-F/wt) for U373R cells was 25.4-fold less than that for parent cells. The expression levels of integrins alpha(v)beta(3) and alpha(v)beta(5) were found to be decreased in U373R cells without affecting the expression levels of Coxsackievirus and adenovirus receptor. The mutant vector AxCAZ2-F/K20, with a linker and a stretch of 20 lysine residues at the COOH-terminal of the fiber protein, improved the transduction efficiency of U373R cells to 12.6-fold of that of AxCAZ2-F/wt. A mutant vector carrying the p53 gene, AxCAhp53-F/K20, dramatically induced apoptosis in U373R cells. CONCLUSIONS: Glioma cells expressing low levels of adenovirus receptors might survive and proliferate to recur after repeated adenoviral transduction, even if the adenoviral transduction is effective at first. Changing the tropism of vectors is a potent method to overcome resistance. 相似文献
105.
Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model 下载免费PDF全文
Shinji Abe Mika Kato Kaneko Yuki Tsuchihashi Toshihiro Izumi Satoshi Ogasawara Naoto Okada Chiemi Sato Makoto Tobiume Kenji Otsuka Licht Miyamoto Koichiro Tsuchiya Kazuyoshi Kawazoe Yukinari Kato Yasuhiko Nishioka 《Cancer science》2016,107(9):1198-1205
Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti‐human podoplanin mAb, NZ‐1, and a rat–human chimeric anti‐human podoplanin antibody, NZ‐8, derived from NZ‐1, which induced antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity against podoplanin‐positive MPM cell lines. In this study, we showed the antitumor effect of NZ‐1, NZ‐8, and NZ‐12, a novel rat–human chimeric anti‐human podoplanin antibody derived from NZ‐1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ‐1 and rat NK (CD161a+) cells inhibited the growth of tumors and the production of pleural effusion in NCI‐H290/PDPN or NCI‐H226 orthotopic xenograft mouse models. NZ‐8 and human natural killer (NK) (CD56+) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ‐12 induced potent ADCC mediated by human MNC, compared with either NZ‐1 or NZ‐8. Antitumor effects were observed following treatment with NZ‐12 and human NK (CD56+) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ‐12 mediated by human NK (CD56+) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin‐targeting immunotherapy using both NZ‐12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. 相似文献
106.
Azusa Tanimoto Tadaaki Yamada Shigeki Nanjo Shinji Takeuchi Hiromichi Ebi Kenji Kita Kunio Matsumoto Seiji Yano 《Oncotarget》2014,5(13):4920-4928
Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK. 相似文献
107.
Downregulation of microRNA‐100/microRNA‐125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion 下载免费PDF全文
Yasuteru Fujino Shunsaku Takeishi Kensei Nishida Koichi Okamoto Naoki Muguruma Tetsuo Kimura Shinji Kitamura Hiroshi Miyamoto Akiko Fujimoto Jun Higashijima Mitsuo Shimada Kazuhito Rokutan Tetsuji Takayama 《Cancer science》2017,108(3):390-397
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR‐100 and miR‐125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real‐time PCR in a larger set of clinical samples. The transfection of a miR‐100 or miR‐125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR‐100 or miR‐125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR‐100‐silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real‐time PCR identified mammalian target of rapamycin (mTOR) and insulin‐like growth factor 1 receptor (IGF1R) as direct, and Fas and X‐linked inhibitor‐of‐apoptosis protein (XIAP) as indirect candidate targets for miR‐100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR‐100 and miR‐125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR‐100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR‐100 and miR‐125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion. 相似文献
108.
BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the most common recurrence diseases, which affects the patient's prognosis. The aim of this report is to evaluate recurrence risk after primary treatment by the combination study with the clinical features and immunohistological findings. METHODS: 153 removable HCCs were examined by immunohistochemical study of the proliferating cell nuclear antigen (PCNA), p53, or Bax. The relationships of these factors with histological grades, the presence of intra-hepatic metastasis (IM), tumor size, value of serum alpha-fetoprotein (AFP), and prognosis were studied. PCNA labeling index (LI) was calculated to count positive nuclei in 1,000 cells. RESULTS: PCNALI was significantly higher in cancer and correlated with tumor size. PCNALI and the tumor diameter in themselves could be a good predictor for patient prognosis and the combination study of them was an even stronger indicator. The value of AFP was significantly higher in positive p53 cases. The incidence of p53 was associated with histological types. The presence of IM was found in negative Bax cases of main tumors. The appearance of Bax was not correlated with histological types. The incidence of p53 or Bax was indicated to distinguish the patient prognosis of the lower grade histological cases, in which differences could not be found by the routine histological study. CONCLUSIONS: The combination study of the immunohistochemical findings and the clinical features could be one of the most important aids in interpreting the status of HCC. 相似文献
109.
Imai H Saio M Nonaka K Suwa T Umemura N Ouyang GF Nakagawa J Tomita H Osada S Sugiyama Y Adachi Y Takami T 《Cancer science》2007,98(3):416-423
Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor-infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population. 相似文献
110.