全文获取类型
收费全文 | 3166篇 |
免费 | 143篇 |
国内免费 | 17篇 |
专业分类
耳鼻咽喉 | 14篇 |
儿科学 | 28篇 |
妇产科学 | 20篇 |
基础医学 | 415篇 |
口腔科学 | 82篇 |
临床医学 | 175篇 |
内科学 | 756篇 |
皮肤病学 | 153篇 |
神经病学 | 172篇 |
特种医学 | 258篇 |
外科学 | 534篇 |
综合类 | 15篇 |
预防医学 | 62篇 |
眼科学 | 14篇 |
药学 | 167篇 |
中国医学 | 6篇 |
肿瘤学 | 455篇 |
出版年
2023年 | 15篇 |
2022年 | 32篇 |
2021年 | 57篇 |
2020年 | 40篇 |
2019年 | 53篇 |
2018年 | 60篇 |
2017年 | 59篇 |
2016年 | 82篇 |
2015年 | 60篇 |
2014年 | 100篇 |
2013年 | 121篇 |
2012年 | 181篇 |
2011年 | 222篇 |
2010年 | 108篇 |
2009年 | 87篇 |
2008年 | 184篇 |
2007年 | 222篇 |
2006年 | 197篇 |
2005年 | 217篇 |
2004年 | 206篇 |
2003年 | 217篇 |
2002年 | 184篇 |
2001年 | 63篇 |
2000年 | 40篇 |
1999年 | 47篇 |
1998年 | 36篇 |
1997年 | 47篇 |
1996年 | 39篇 |
1995年 | 32篇 |
1994年 | 27篇 |
1993年 | 22篇 |
1992年 | 37篇 |
1991年 | 26篇 |
1990年 | 28篇 |
1989年 | 31篇 |
1988年 | 16篇 |
1987年 | 21篇 |
1986年 | 16篇 |
1985年 | 6篇 |
1984年 | 14篇 |
1983年 | 8篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1971年 | 5篇 |
1969年 | 3篇 |
1968年 | 3篇 |
1967年 | 4篇 |
排序方式: 共有3326条查询结果,搜索用时 15 毫秒
1.
Keiko Goto Yutaka Fujiwara Takeshi Isobe Naoko Chayahara Naomi Kiyota Toru Mukohara Yukari Tsubata Takamasa Hotta Kenji Tamura Noboru Yamamoto Hironobu Minami 《Cancer science》2019,110(6):1987-1994
Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m2), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m2), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m2), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m2). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe. 相似文献
2.
Taisuke Inada Satoshi Fukushima Masayuki Murai Masatoshi Jinnin Azusa Miyashita Satoshi Nakahara Junji Yamashita Jun Aoi Shinichi Masuguchi Hironobu Ihn 《The Journal of dermatology》2015,42(2):198-201
miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma. 相似文献
3.
Regional fractional ventilation mapping in spontaneously breathing mice using hyperpolarized 129Xe MRI 下载免费PDF全文
Hirohiko Imai Hironobu Matsumoto Erika Miyakoshi Shintaro Okumura Hideaki Fujiwara Atsuomi Kimura 《NMR in biomedicine》2015,28(1):24-29
The feasibility of ventilation imaging with hyperpolarized (HP) 129Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP 129Xe delivered continuously from a 129Xe polarizer. A series of 129Xe ventilation images was obtained by varying the number of breaths before the 129Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE‐treated group. The whole‐lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE‐treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
4.
Akira Sugawara Kazuhisa Takeuchi Takashi Suzuki Keiichi Itoi Hironobu Sasano Sadayoshi Ito 《Hypertension research》2003,26(8):663-668
We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent. 相似文献
5.
Kiyotaka YOH Makoto TAHARA Kenji KAWADA Hirofumi MUKAI Masanobu NAKATA Kuniaki ITOH Mitsuhiko KAWASHIMA Hideki NISHIMURA Ryuichi HAYASHI Takashi OGINO Hironobu MINAMI 《Asia-Pacific Journal of Clinical Oncology》2006,2(4):180-184
Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation. 相似文献
6.
Hironobu Ishiyama Makoto Sato Kuniko Matsumura Miwa Sento Keiki Ogino Tatsuya Hobara 《Basic & clinical pharmacology & toxicology》1995,77(4):293-298
Abstract: Intravenous injection of gadolinium chloride (GdCl3) at a dose of 10 mg/kg caused an increase in proliferating cell nuclear antigen labeling index and the grade of pyronin positivity (RNA level) in rat liver. In CCl4-exposed rats, pretreatment with GdCl3 also showed a preventive effect of the liver injury both biochemically and histologically. Moreover, the proliferative action preceded the attenuative effect of the liver injury. Results suggest that GdCl3 induces hepatocyte proliferation, and this action of GdCl3 may modify the development of CCl4-induced liver injury. 相似文献
7.
8.
Hui Liu Tetsuzo Agishi Hideiku Suga Yutaro Hayasaka Satoshi Teraoka Kazuo Ota 《Artificial organs》1995,19(4):324-327
Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation. 相似文献
9.
Masafumi Fujimoto Tuneaki Sakata Yuji Tsuruta Shoji Iwagami Hiroshi Teraoka Shin-ichi Mihara Yonetaka Fukiishi Misao Ide 《Biochemical pharmacology》1990,40(12):2661-2670
Bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells was enhanced by pretreatment of the cells with pertussis toxin or islet-activating protein (IAP) for 5 hr or longer. Although ADP-ribosylation of a protein with a molecular weight of 41–42 kD in the cell membranes was completed by 3 hr after the addition of IAP into the incubation medium, there was good correlation between enhancement of bradykinin-induced prostacyclin synthesis and ADP-ribosylation of the IAP substrate over a wide range of IAP concentrations. Furthermore, even if IAP was removed from the incubation medium at 3 hr, bradykinin-induced prostaglandin synthesis at 24 hr was still potentiated. Cycloheximide and actinomycin D enhanced bradykinin-induced prostacyclin synthesis and apparently blocked the effect of IAP. Since this result suggested the involvement of an inhibitor protein(s) of prostacyclin synthesis in the IAP effect, we studied the effect of IAP on the level of lipocortin I which is known to inhibit phospholipase A2. Western and Northern blot analyses revealed that IAP decreased the amounts of protein and mRNA of lipocortin I. These results suggest that the enhancement of bradykinin-induced prostacyclin synthesis by IAP is associated with a decrease in the level of lipocortin I. 相似文献
10.
Kohei Hara MD PhD Shigeru Kohno MD PhD Hironobu Koga MD PhD 《Journal of infection and chemotherapy》1996,1(3):166-176
Conclusion Reviewing the history of diagnostic procedures of causative organisms of respiratory infections, invasive techniques such
as the protected specimen catheter (PSB) and bronchoalveolar lavage (BAL) have become the preferred choices because they have
many advantages. These methods cause the patient relatively little discomfort, and permit an early diagnosis since they can
easily be performed at the bedside and the causative organism from the disease site is obtained in cultures. These procedures
can be used not only in patients with community-acquired lung infections, but also in immunocompromised hosts, including those
with blood diseases or following renal transplantation, in patients in intensive care units and in mechanically-ventilated
patients so that the cause can be accurately determined and chemotherapy started quickly, resulting in better therapeutic
efficacy.
Although these invasive procedures are advantageous for the diagnosis of respiratory infections, they also present various
problems which remain to be addressed including minimizing contamination and setting diagnostic threshold values. However,
the importance of accurately determining the causative organism in respiratory infections should be recognized as the most
important factor, and these methods have shown to date to provide the most accurate information to aid in the timely treatment
of respiratory infections in a wide variety of patients. 相似文献