全文获取类型
收费全文 | 10914篇 |
免费 | 469篇 |
国内免费 | 77篇 |
专业分类
耳鼻咽喉 | 93篇 |
儿科学 | 227篇 |
妇产科学 | 84篇 |
基础医学 | 1419篇 |
口腔科学 | 225篇 |
临床医学 | 638篇 |
内科学 | 2861篇 |
皮肤病学 | 128篇 |
神经病学 | 653篇 |
特种医学 | 377篇 |
外科学 | 2010篇 |
综合类 | 58篇 |
预防医学 | 264篇 |
眼科学 | 186篇 |
药学 | 558篇 |
中国医学 | 50篇 |
肿瘤学 | 1629篇 |
出版年
2024年 | 10篇 |
2023年 | 90篇 |
2022年 | 172篇 |
2021年 | 277篇 |
2020年 | 144篇 |
2019年 | 188篇 |
2018年 | 256篇 |
2017年 | 181篇 |
2016年 | 265篇 |
2015年 | 221篇 |
2014年 | 331篇 |
2013年 | 384篇 |
2012年 | 689篇 |
2011年 | 706篇 |
2010年 | 435篇 |
2009年 | 354篇 |
2008年 | 693篇 |
2007年 | 738篇 |
2006年 | 702篇 |
2005年 | 749篇 |
2004年 | 688篇 |
2003年 | 639篇 |
2002年 | 686篇 |
2001年 | 114篇 |
2000年 | 108篇 |
1999年 | 143篇 |
1998年 | 188篇 |
1997年 | 152篇 |
1996年 | 121篇 |
1995年 | 119篇 |
1994年 | 94篇 |
1993年 | 99篇 |
1992年 | 75篇 |
1991年 | 94篇 |
1990年 | 67篇 |
1989年 | 78篇 |
1988年 | 77篇 |
1987年 | 60篇 |
1986年 | 36篇 |
1985年 | 26篇 |
1984年 | 30篇 |
1983年 | 25篇 |
1982年 | 21篇 |
1981年 | 23篇 |
1980年 | 23篇 |
1979年 | 7篇 |
1978年 | 13篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1970年 | 8篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
Kenya Kusunose Yuichiro Okushi Yoshihiro Okayama Robert Zheng Miho Abe Michikazu Nakai Yoko Sumita Takayuki Ise Takeshi Tobiume Koji Yamaguchi Shusuke Yagi Daiju Fukuda Hirotsugu Yamada Takeshi Soeki Tetsuzo Wakatsuki Masataka Sata 《Nutrients》2021,13(2)
A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials. 相似文献
102.
Takuya Sekiguchi Yoshihiro Hagiwara Akira Ando Kenji Kanazawa Kazuaki Suzuki Masashi Koide Yutaka Yabe Satsuki Onoda Eiji Itoi 《Journal of orthopaedic science》2021,26(4):595-598
BackgroundThe Shoulder Pain and Disability Index (SPADI) is a simple disease specific questionnaire that is used to evaluate the impact of shoulder disorders. The purpose of this study was to translate the SPADI into Japanese (SPADI-Jp) and evaluate its reliability and validity in Japanese patients with shoulder disorders.MethodsCross-cultural adaptation of the SPADI was performed according to international guidelines. A total of 100 patients with shoulder disorders participated in this study. Each participant was asked to finish the SPADI-Jp, Disability of Arm, Shoulder and Hand (DASH), and the Short-Form 36 (SF-36) at the initial visit. Thirty-four patients repeated the SPADI-Jp to assess the test–retest reliability. The test–retest reliability was quantified using the interclass correlation coefficient (ICC), while Cronbach's alpha was calculated to assess the internal consistency. The construct validity was assessed using Spearman's rank correlation coefficients.ResultsInternal consistency in the SPADI-Jp was very high (0.969), as measured by the Cronbach's alpha. The ICC of the SPADI-Jp was 0.930. There was a strong, positive correlation between the DASH and the SPADI-Jp (r = 0.837, p < 0.001). The SPADI-Jp was significantly correlated with most of the SF-36 subscales. The correlations of the SPADI-Jp with physical subscales of the SF-36 were stronger than those with the other subscales.ConclusionsWe demonstrated that the SPADI-Jp is a reliable and valid self-assessment tool. Because cross-cultural adaptation, validation, and reliability of the disease-specific questionnaire for shoulder pain and disability have not been evaluated in Japan, the SPADI-Jp can be useful for evaluating such patients in the Japanese population. 相似文献
103.
Hideyuki Arima Yu Yamato Kimihito Sato Yoshihiro Uchida Toshiyuki Tsuruta Kanehisa Hashiguchi Hajime Hamamoto Eiichiro Watanabe Kaoru Yamanaka Tomohiko Hasegawa Go Yoshida Tatsuya Yasuda Tomohiro Banno Shin Oe Hiroki Ushirozako Tomohiro Yamada Koichiro Ide Yuh Watanabe Yukihiro Matsuyama 《Journal of orthopaedic science》2021,26(4):577-583
BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ 相似文献
104.
Wada Takehiko Ishimoto Takuji Nakaya Izaya Kawaguchi Takehiko Sofue Tadashi Shimizu Sayaka Kurita Noriaki Sasaki Sho Nishiwaki Hiroki Koizumi Masahiro Saito Shoji Nishibori Nobuhiro Oe Yuji Yoshida Mai Miyaoka Yoshitaka Akiyama Shin’ichi Itano Yuya Okazaki Masaki Ozeki Takaya Ichikawa Daisuke Oguchi Hideyo Kohsaka Satoshi Kosaka Shiho Kataoka Yuki Shima Hideaki Shirai Sayuri Sugiyama Kazuhiro Suzuki Tomo Son Daisuke Tanaka Tomomi Nango Eishu Niihata Kakuya Nishijima Yoko Nozu Kandai Hasegawa Midori Miyata Rei Yazawa Masahiko Yamamoto Yoshihiro Yamamoto Ryohei Shibagaki Yugo Furuichi Kengo Okada Hirokazu Narita Ichiei 《Clinical and experimental nephrology》2021,25(12):1277-1285
Clinical and Experimental Nephrology - 相似文献
105.
106.
Yoshihiro Mitsuhashi Yuichi Sugiyama Shogo Ozawa Takashi Nitanai Kunihiro Sasahara Kan-Ichi Nakamura Miroru Tanaka Takuzo Nishimura Makoto Inaba Tomowo Kobayashi 《Cancer chemotherapy and pharmacology》1990,27(1):20-26
Summary Plasma concentration-time profiles of nimustine hydrochloride, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), in the mouse, rat, rabbit, and dog were determined by high-performance liquid chromatographic analysis. The pharmacokinetic parameters for these four animal species and previously reported clinical data were analyzed for investigation of interspecies correlation. Loglog plots of body weight (W; kg) vs total plasma clearance (CLtot, p; ml/min) and steady-state distribution volume (Vd, ss; 1) for the four animal species were linear, with high correlation coefficients (r 0.996 for both parameters), despite the fact that the nonrenal clearance was >97% in these species. Linear regression on the plots excluding human data yielded allometric equations (CLtot,p=50.6 W0.957; Bd, ss=1.29 W1.03) that were extrapolated to predict ACNU pharmacokinetic parameters in humans. For both parameters, however, there were 3-fold differences between the predicted and observed parametric values. To investigate these discrepancies, we measured serum protein binding of ACNU in these animal species and in humans. The values of CLtot,p and Vd,ss were converted into those of CLu
tot,p and Vd,u
ss, which correspond to the parameters for unbound ACNU. In this case, correlation coefficients of the log-log plots excluding human data (CLu
tot,p=71.7 W0.891; Bd,u
ss=1.82 W0.966) were also high (r0.991). The extrapolated values vs those observed in a 70-kg human were the following: CLu
tot,p, 3,160 vs 2,290 ml/min; Vd,u
ss, 110 vs 1061. Thus, the animal data were successfully extrapolated to yield better predictions of human pharmacokinetic parameters if the analysis was based on the unbound plasma concentration of ACNU. In addition, the predicted plasma concentration-time profile for humans also showed good agreement with the observed ones. These results suggest the importance of measuring unbound fractions of drugs for more accurate prediction of human pharmacokinetic parameters by extrapolation of animal data to the human situation. 相似文献
107.
We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman
who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant.
The tumor was elastic and soft, smooth surfaced, well-defined and mobile. Dimpling sign or change of skin color were not observed.
Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended
surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin
and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in
the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of
angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the
cervical and thoracic vertebrae were observed and radiation therapy was performed. Sixteen months from onset, she died due
to multi-organ failure as general metastases of angiosarcoma. At autopsy, metastases to many organs including the digestive
system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized
the difficulties in clinical diagnosis and treatment for the angiosarcoma of the breast. 相似文献
108.
Toru Watanabe Noriko Kokubu Steven B Charnick Mikihiko Naito Takashi Tsuruo Dalia Cohen 《British journal of pharmacology》1997,122(2):241-248
- P-glycoprotein, a 170–180 kDa membrane glycoprotein that mediates multidrug resistance, hydrolyses ATP to efflux a broad spectrum of hydrophobic agents. In this study, we analysed the effects of three MDR reversing agents, verapamil, cyclosporin A and [3′-keto-Bmt]-[Val*]-cyclosporin (PSC 833), on the adenosine triphosphatase (ATPase) activity of human P-glycoprotein.
- P-glycoprotein was immunoprecipitated with a monoclonal antibody (MRK-16) and the P-glycoprotein-MRK-16-Protein A-Sepharose complexes obtained were subjected to a coupled enzyme ATPase assay.
- While verapamil activated the ATPase, the cyclosporin derivatives inhibited both the substrate-stimulated and the basal P-glycoprotein ATPase. No significant difference was observed between PSC 833 and cyclosporin A on the inhibition of basal P-glycoprotein ATPase activity. PSC 833 was more potent than cyclosporin A for the substrate-stimulated activity.
- Kinetic analysis indicated a competitive inhibition of verapamil-stimulated ATPase by PSC 833.
- The binding of 8-azido-[α-32P]-ATP to P-glycoprotein was not altered by the cyclosporin derivatives, verapamil, vinblastine and doxorubicin, suggesting that the modulation by these agents of P-glycoprotein ATPase cannot be attributed to an effect on ATP binding to P-glycoprotein.
- The interaction of the cyclosporin derivatives with ATPase of P-glycoprotein might present an alternative and/or additional mechanism of action for the modulation of P-glycoprotein function.
109.
Toshiro Takatori Takeshi Koizumi Taro Tokui Yoshihiro Mitsuhashi Akio Shiraishi Takashi Tsuruo 《Cancer chemotherapy and pharmacology》1995,35(4):283-290
RS-1541, an acyl-derivative of rhizoxin (Fig. 1), is a potent antitumor compound. This agent showed cytotoxicity in vitro on some cultured human tumor cells, although it was less potent than rhizoxin. Rhizoxin exhibited antitumor effects by inhibiting the polymerization of tubulin, whereas RS-1541 did not inhibit tubulin polymerization in vitro. However, cell cycle analysis in vivo showed that the two agents had the same mode of action. The cytotoxicity of RS-1541 was enhanced when the initial cell density of the cells was increased. The cytotoxicity was also enhanced when the membrane fraction of St-4 cells, which were the most sensitive to RS-1541 among the cell lines tested, was added to the target cells. When St-4 cells were incubated with [14C]-RS-1541, significant amounts of [14C]-rhizoxin were produced within the cells. Further fractionation of the crude membrane showed that the activity that enhanced the cytotoxicity of RS-1541 (RS-1541-enhancing activity) belonged to the mitochondrial-lysosomal fraction, not to the microsomal fraction. Both the enhancing activity and the activity that converting [14C]-RS-1541 to [14C]-rhizoxin (RS-1541-converting activity) were inhibited by treatment with chloroquine, an inhibitor of lysosomal function. Cholesterol esterase derived fromCandida cylindracea had RS-1541-enhancingand-converting activities. These data suggest that RS-1541 exerts its cytotoxic action after being converted to rhizoxin within the cells by a lysosomal enzyme such as cholesterol esterase.Abbreviations
DMSO
Dimethylsulfoxide
-
PBS(-) Ca2+
Mg2+-free phosphate-buffered saline
-
HCO60
hydrogenated castor oil polyethylene glycor ether
-
DMA
dimethylacetamide
-
RSB
reticulocyte standard buffer, consisting of 10mM NaCl, 1.5 mM MgCl2, and 10 mM TRIS-HCl, (pH 7.4)
-
TLC
thin-layer chromatography
-
ara-C
1--D-arabinofuranosylcytosine
-
LDL
low-density lipoprotein 相似文献
110.
Wei-dong Zhang Masataka Nagao Takehiko Takatori Kimiharu Iwadate Yoshiyuki Itakura Yoshihiro Yamada Hirotaro Iwase Tsuneaki Oono 《International journal of legal medicine》1995,107(4):174-178
This paper investigates the immunohistochemical dynamics of leukotoxin (9,10-epoxy-12-octadecenoic acid, LTx) in the lungs of rats exposed to hyperoxia with or without paraquat. The rats were treated with 100% oxygen or ambient air for 24. 48, 72 and 96 h in the presence or absence of a low or high dose paraquat (1,1-di-methyl-4,4-bipyridinium, PQ) injection. Immunostaining for LTx demonstrated positive reactions in the neutrophils that showed a progressive increase in intensity of staining with time in all groups exposed to 100% oxygen and in the group with high dose PQ, but the positive findings were weak in the group injected with low dose PQ only. We found the positive immunostaining reaction not only in neutrophils but also in alveolar macrophages. This indicates that LTx is produced by alveolar macrophages as well as by neutrophils depending on the treatment period under hyperoxic conditions, suggesting that LTx is an important chemical mediator in pulmonary diseases. 相似文献