全文获取类型
收费全文 | 5767篇 |
免费 | 340篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 20篇 |
儿科学 | 168篇 |
妇产科学 | 135篇 |
基础医学 | 755篇 |
口腔科学 | 94篇 |
临床医学 | 349篇 |
内科学 | 1492篇 |
皮肤病学 | 196篇 |
神经病学 | 386篇 |
特种医学 | 198篇 |
外科学 | 1118篇 |
综合类 | 13篇 |
预防医学 | 140篇 |
眼科学 | 64篇 |
药学 | 261篇 |
中国医学 | 2篇 |
肿瘤学 | 742篇 |
出版年
2023年 | 48篇 |
2022年 | 101篇 |
2021年 | 154篇 |
2020年 | 68篇 |
2019年 | 95篇 |
2018年 | 132篇 |
2017年 | 108篇 |
2016年 | 137篇 |
2015年 | 157篇 |
2014年 | 163篇 |
2013年 | 218篇 |
2012年 | 370篇 |
2011年 | 407篇 |
2010年 | 208篇 |
2009年 | 210篇 |
2008年 | 382篇 |
2007年 | 351篇 |
2006年 | 428篇 |
2005年 | 357篇 |
2004年 | 380篇 |
2003年 | 379篇 |
2002年 | 365篇 |
2001年 | 65篇 |
2000年 | 46篇 |
1999年 | 61篇 |
1998年 | 89篇 |
1997年 | 87篇 |
1996年 | 80篇 |
1995年 | 59篇 |
1994年 | 60篇 |
1993年 | 55篇 |
1992年 | 29篇 |
1991年 | 49篇 |
1990年 | 28篇 |
1989年 | 22篇 |
1988年 | 19篇 |
1987年 | 8篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 10篇 |
1981年 | 14篇 |
1980年 | 5篇 |
1978年 | 6篇 |
1973年 | 5篇 |
1958年 | 12篇 |
1957年 | 9篇 |
1956年 | 13篇 |
1955年 | 9篇 |
1954年 | 10篇 |
排序方式: 共有6133条查询结果,搜索用时 15 毫秒
991.
992.
993.
Junko Tanizaki Koji Haratani Hidetoshi Hayashi Yasutaka Chiba Yasushi Nakamura Kimio Yonesaka Keita Kudo Hiroyasu Kaneda Yoshikazu Hasegawa Kaoru Tanaka Masayuki Takeda Akihiko Ito Kazuhiko Nakagawa 《Journal of thoracic oncology》2018,13(1):97-105
Objective
The aim of this study was to identify baseline peripheral blood biomarkers associated with clinical outcome in patients with NSCLC treated with nivolumab.Methods
Univariable and multivariable analyses were performed retrospectively for 134 patients with advanced or recurrent NSCLC treated with nivolumab to evaluate the relationship between survival and peripheral blood parameters measured before treatment initiation, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and absolute eosinophil count (AEC), as well as serum C-reactive protein and lactate dehydrogenase levels. Progression-free survival, overall survival, and response rate were determined.Results
Among the variables selected by univariable analysis, a low ANC, high ALC, and high AEC were significantly and independently associated with both better progression-free survival (p = 0.001, p = 0.04, and p = 0.02, respectively) and better overall survival (p = 0.03, p = 0.03, and p = 0.003, respectively) in multivariable analysis. Categorization of patients according to the number of favorable factors revealed that those with only one factor had a significantly worse outcome than those with two or three factors. A similar trend was apparent for patients with a programmed death 1 ligand tumor proportion score less than 50%, whereas all patients with a score of 50% or higher had at least two favorable factors.Conclusions
A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate. 相似文献994.
Naoki Niikura Akihiko Shimomura Yumi Fukatsu Masataka Sawaki Rin Ogiya Hiroyuki Yasojima Tomomi Fujisawa Mitsugu Yamamoto Michiko Tsuneizumi Akira Kitani Junichiro Watanabe Akira Matsui Yuko Takahashi Seiki Takashima Tadatoshi Shien Kenji Tamura Shigehira Saji Norikazu Masuda Yutaka Tokuda Hhiroji Iwata 《Breast cancer research and treatment》2018,167(1):81-87
Purpose
Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.Methods
We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.Results
The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor’s recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).Conclusion
We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.995.
Ishida Yuko Kuninaka Yumi Furukawa Fukumi Kimura Akihiko Nosaka Mizuho Fukami Mie Yamamoto Hiroki Kato Takashi Shimada Emi Hata Satoshi Takayasu Tatsunori Eisenmenger Wolfgang Kondo Toshikazu 《International journal of legal medicine》2018,132(1):237-242
International Journal of Legal Medicine - Immunohistochemical investigation of aquaporin (AQP)1 and AQP3 was performed in human skin wounds obtained from forensic autopsy cases. A total of 55 human... 相似文献
996.
Phase I study of taselisib in Japanese patients with advanced solid tumors or hormone receptor‐positive advanced breast cancer
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kenji Tamura Makoto Kodaira Chikako Shimizu Kan Yonemori Mayu Yunokawa Akihiko Shimomura Takayuki Kobayashi Kenji Nakano Junichi Tomomatsu Yoshinori Ito Jun Tanaka Hiroshi Kuriki Zhaodi Gu Shunji Takahashi 《Cancer science》2018,109(5):1592-1601
Taselisib is a potent and selective phosphatidylinositide 3‐kinase (PI3K) inhibitor. The present article reports the first study of taselisib administration in Japanese patients. The aim of this 2‐stage, phase I, multicenter, open‐label, dose‐escalation study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of taselisib as monotherapy in Japanese patients with advanced solid tumors (stage 1), and as part of combination therapy in Japanese patients with hormone receptor (HR)‐positive locally advanced or recurrent breast cancer (stage 2). In stage 1, oral taselisib tablets 2, 4, and 6 mg/d were given in 28‐day cycles. In stage 2, successive cohorts of patients received oral taselisib tablets (2 or 4 mg/d) with i.m. fulvestrant 500 mg. Nine and 6 patients were enrolled in stage 1 and stage 2, respectively. Taselisib was well tolerated. No dose‐limiting toxicities were experienced in any cohort of patients and no deaths were observed. The most common treatment‐related adverse events in stage 1 and stage 2, respectively, were rash (55.6%, 66.7%), diarrhea (44.4%, 66.7%), and stomatitis (44.4%, 66.7%). Taselisib was rapidly absorbed after dosage; its half‐life was 12.9‐32.0 hours in stage 1 and 16.1‐26.5 hours in stage 2. Two patients achieved partial response (PR), 5 patients had stable disease (SD) and 2 patients had progressive disease (PD) in stage 1, and 1 patient had PR and 3 patients had SD in stage 2. All patients with PR were positive for PIK3CA gene mutations. These preliminary data suggest that taselisib may be effective in patients with PIK3CA‐mutated solid tumors or HR‐positive advanced breast cancer. 相似文献
997.
Generation and application of human induced‐stem cell memory T cells for adoptive immunotherapy
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Taisuke Kondo Yuki Imura Shunsuke Chikuma Sana Hibino Setsuko Omata‐Mise Makoto Ando Takashi Akanuma Mana Iizuka Ryota Sakai Rimpei Morita Akihiko Yoshimura 《Cancer science》2018,109(7):2130-2140
Adoptive T‐cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen‐specific stem cell memory T (TSCM) cells is expected to overcome this shortcoming as TSCM cells are close to naïve T cells, but are also highly proliferative, long‐lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into TSCM‐like cells (iTSCM) by coculturing with OP9 cells expressing Notch ligand, Delta‐like 1 (OP9‐hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti‐CD3/CD28 antibodies or by antigen‐presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9‐hDLL1 cells, interleukin (IL)‐7 and IL‐15 (but not IL‐2 or IL‐21) could efficiently generate iTSCM cells. Epstein–Barr virus‐specific iTSCM cells showed much stronger antitumor potentials than conventionally activated T cells in humanized Epstein–Barr virus transformed‐tumor model mice. Thus, adoptive T‐cell therapy with iTSCM offers a promising therapeutic strategy for cancer immunotherapy. 相似文献
998.
Yukawa K Hoshino K Kishino M Mune M Shirasawa N Kimura A Tsubota Y Owada-Makabe K Tanaka T Ichinose M Maeda M Takeda K Akira S 《International journal of molecular medicine》2004,13(4):515-520
Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent serine/threonine kinase that has been implicated as a positive mediator of apoptosis. However, little is known about the involvement of DAPK in the apoptosis associated with several pathological states, except for cancer. Here, DAPK-mutant mice were used in order to examine the role of DAPK in renal cell apoptosis in chronic obstructive uropathy (COU) created by unilateral ureteral ligation. These mice express mutant DAPK with a deletion of 74 amino acids from the catalytic kinase domain. Obstructed kidneys in wild-type and mutant mice were examined for both DAPK protein levels and renal cell apoptosis during the course of COU. Obstructed kidneys in wild-type and mutant mice showed a marked increase in the DAPK and mutant DAPK protein levels, respectively, at day 14 after ureteric ligation. The obstructed kidneys in DAPK-mutant mice displayed a significant attenuation of tubular cell apoptosis, compared with wild-type mice. In contrast, no significant difference in interstitial cell apoptosis was observed between the obstructed kidneys from wild-type and mutant mice. Thus, these results indicate that the part of the kinase domain deleted by the gene targeting is crucial for the execution of tubular cell apoptosis, but is not essential for interstitial cell apoptosis in a COU model in mice. 相似文献
999.
Nano-scale modification of a segmented polyurethane (SPU) with cross-linked 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer was performed to obtain a biocompatible elastomer. To control the domain size and the depth of the modified layer, various compositions of monomers, including MPC, 2-ethylhexyl methacrylate (EHMA), and glycerol 1,3-diglycerolate diacrylate, were examined. SPU film was immersed in the monomer solution and visible light irradiation was applied to initiate polymerization to the SPU film that was held by mica to condense MPC units at the surface. The surfaces of the obtained film were analyzed by X-ray photoelectron spectroscopy and water contact angle measurement. The surface density of MPC units changed with the monomer concentration, and the density was the highest when the ratio between MPC and EHMA was 7:3. In modified SPU films, 6- to 25-nm MPC unit-enriched domains were observed and the density of these domains gradually decreased with depth. The sizes of the domains depended on the MPC composition in the monomer solution. The mechanical properties of the modified films as evaluated by tensile strength measurement under wet conditions were not significantly different from those of SPU. With increase in the existence of MPC unit-enriched domains on the MEG film surface, platelet adhesion and activation were remarkably reduced compared to the SPU film. This nano-scale surface modification may be a useful technique for applying elastic polymer biomaterials. 相似文献
1000.
Kawahara K Kimura A Okagaki A Fujita Y Kawano A Hayashi T Oohashi S Todo R Kurata A Kusuoka H 《Rinsho byori. The Japanese journal of clinical pathology》2002,50(6):630-634
Effective and rapid use of cytological data are issue in Japan. We addressed this problem by development of an ordering system for cytological examinations at Osaka National Hospital. This system is located in the department of pathology and is a client-server system that consisted of 1 server and 6 clients. Five of the 6 clients are related to cytology and there are connections to microscopes with digital cameras. One client is for acceptance of cytological specimens at the department of pathology. Through a local area network, 100 Mbps, this system is connected to the hospital information system, which is of the order-entry type. After a clinician orders a cytological examination, these data are sent to both the Accounts and Pathology departments. A small bar-code label is simultaneously printed out, which is stuck on the form. By checking this label at the department of pathology by using a label reader, relevant clinical information is sent to the pathology server. After the cytological diagnosis has been made by senior cytotechnologist and cytopathologist, data on the diagnosis and microscopic images are sent to the hospital information system. Thus, clinicians can review the cytological diagnosis together with the photomicrographs. This new cytology system has brought great benefits to both cytotechnologist and clinicians with regard to the rapid transfer of cytological examination, and it seems to contribute to more advanced and efficient medical care. 相似文献