全文获取类型
收费全文 | 6640篇 |
免费 | 403篇 |
国内免费 | 40篇 |
专业分类
耳鼻咽喉 | 79篇 |
儿科学 | 170篇 |
妇产科学 | 144篇 |
基础医学 | 1032篇 |
口腔科学 | 134篇 |
临床医学 | 473篇 |
内科学 | 1654篇 |
皮肤病学 | 265篇 |
神经病学 | 585篇 |
特种医学 | 167篇 |
外科学 | 587篇 |
综合类 | 29篇 |
预防医学 | 347篇 |
眼科学 | 159篇 |
药学 | 542篇 |
中国医学 | 24篇 |
肿瘤学 | 692篇 |
出版年
2024年 | 4篇 |
2023年 | 45篇 |
2022年 | 115篇 |
2021年 | 175篇 |
2020年 | 97篇 |
2019年 | 183篇 |
2018年 | 178篇 |
2017年 | 149篇 |
2016年 | 172篇 |
2015年 | 185篇 |
2014年 | 244篇 |
2013年 | 302篇 |
2012年 | 502篇 |
2011年 | 516篇 |
2010年 | 291篇 |
2009年 | 255篇 |
2008年 | 414篇 |
2007年 | 471篇 |
2006年 | 482篇 |
2005年 | 483篇 |
2004年 | 443篇 |
2003年 | 383篇 |
2002年 | 409篇 |
2001年 | 60篇 |
2000年 | 39篇 |
1999年 | 58篇 |
1998年 | 77篇 |
1997年 | 60篇 |
1996年 | 51篇 |
1995年 | 36篇 |
1994年 | 39篇 |
1993年 | 26篇 |
1992年 | 14篇 |
1991年 | 17篇 |
1990年 | 17篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 10篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有7083条查询结果,搜索用时 0 毫秒
41.
Takashi Ueno Akira Tangoku Shigefumi Yoshino Toshihiro Abe Hideto Hayashi Hiroaki Toshimitsu Kiichiro Hashimoto Tomomitsu Satoh Atsunori Oga Tomoko Furuya Masaaki Oka Kohsuke Sasaki 《Clinical cancer research》2003,9(14):5137-5141
PURPOSE: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. EXPERIMENTAL DESIGN: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). RESULTS: Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. CONCLUSIONS: Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen. 相似文献
42.
A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities
comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included
ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing
of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation
of clinical and radiological findings in the present patient do not fit any known malformation syndrome.
Received: 14 February 1998 Accepted: 15 June 1998 相似文献
43.
Increased Sensitivity to Long-term 5-Fluorouracil Exposure of Human Colon Cancer HT-29 Cells Resistant to Short-term Exposure 总被引:3,自引:1,他引:3
A 5-fluorouracil (5-FU)-resistant subline of human colon cancer HT-29 cells was developed by repeated 1-h exposure in vitro to 5-FU. This subline (HT-29/5-FU/S) had 8-fold resistance to 5-FU in a 1-h exposure assay. However, it had rather increased sensitivity to 5-FU when assayed after a continuous 96-h exposure to it. Significantly less 5-fluorouridine-5'-triphosphate was produced in the resistant cells, leading to a lower level of 5-FU incorporation into the cellular RNA. The reduced activity of orotate phosphoribosyltransferase might explain these results. In contrast, the HT-29/5-FU/S cells were more sensitive to the inhibition of in situ thymidylate synthase (TS) by 5-FU than were the parent cells. The lower in situ TS activity may have made HT-29/5-FU/S cells more sensitive to TS inhibition by 5-FU as compared with the parent cells. The fact that HT-29/5-FU/S was more resistant to short-term 5-FU exposure but more sensitive to long-term exposure than the parent line confirmed the existence of different modes of action of 5-FU, depending on the exposure time. 相似文献
44.
Tomoko Ohtsu Hirofumi Fujii Hisashi Wakita Tadahiko Igarashi Kuniaki Itoh Shigeru Imoto Masahiro Kohagura Yasutsuna Sasaki 《Cancer chemotherapy and pharmacology》1998,42(1):1-8
The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA)
as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and
14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition,
multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured
by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day
1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax),
area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more
frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital,
dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations
were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present
we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view.
Received: 2 May 1997 / Accepted: 13 October 1997 相似文献
45.
46.
Sachiko Iwai Tomoko Hasegawa Hanako Ohashi Ikeda Akitaka Tsujikawa 《Investigative ophthalmology & visual science》2022,63(9)
PurposeWe have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.MethodsIntracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.ResultsBCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.ConclusionsBCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration. 相似文献
47.
Hiroyuki Ito Kiyoko Ito Mahika Tanaka Mayumi Hokamura Mari Tanaka Eiji Kusano Jiro Kondo Takuma Izutsu Suzuko Matsumoto Hideyuki Inoue Shinichi Antoku Tomoko Yamasaki Toshiko Mori Michiko Togane 《Internal medicine (Tokyo, Japan)》2022,61(9):1309
Objective Diabetes is recognized as an underlying disease of constipation. However, the prevalence of constipation varies according to the diagnostic criteria applied. We investigated the prevalence of constipation based on the new guideline for constipation in Japanese patients with type 2 diabetes and examined the relationship with the clinical background, including diabetic vascular complications. Methods Questionnaire surveys including items concerning the diagnosis and treatment status of constipation were administered to 410 patients with type 2 diabetes. Results Although 29% of the patients considered that they had experienced constipation (self-judged), only 14% had consulted a physician about constipation. The prevalence of chronic constipation based on the guideline was 26%. After including laxative users, constipation was finally found in 36%. Despite the use of laxatives (n=81), 51% of the patients were still diagnosed with chronic constipation. Patients with constipation (chronic constipation or laxative use) were significantly older and had a longer duration of diabetes than those without constipation. The body mass index (BMI) of patients with constipation (24.9±3.8 kg/m2) was significantly lower than that of those without constipation (26.3±4.6 kg/m2). Diabetic neuropathy (49% vs. 32%) and coronary heart disease (CHD) (27% vs. 13%) were significantly more frequent in the patients with constipation than in those without constipation. A multivariate logistic regression analysis revealed that gender, BMI, diabetic neuropathy, insulin use, and CHD were significantly associated with constipation. Conclusion An accurate diagnosis of constipation is desirable in patients with type 2 diabetes because constipation is independently associated with CHD. 相似文献
48.
Aiko Terakawa Ryotaro Bouchi Noriko Kodani Tomoko Hisatake Takehiro Sugiyama Michihiro Matsumoto Noriko IhanaSugiyama Mitsuru Ohsugi Kohjiro Ueki Hiroshi Kajio 《Journal of diabetes investigation.》2022,13(6):1094
AimTo investigate (1) the association of lifestyle changes and living and working conditions with glycemic control and (2) whether treatment was intensified appropriately in patients with diabetes under the first COVID‐19 state of emergency in Japan.Materials and MethodsA total of 321 participants were included. Participants completed a questionnaire regarding lifestyle changes, including diet, physical activity, and living and working conditions during the COVID‐19 pandemic. The change in hemoglobin A1c (HbA1c) levels was estimated before (June 1, 2019 to August 31, 2019) and during (June 1, 2020 to August 31, 2020) the pandemic. Factors associated with changes in HbA1c levels were examined by multiple linear regression analysis. The proportion of patients who received treatment intensification for diabetes was compared between before and during the pandemic.ResultsThere was no significant change in HbA1c levels before the pandemic and during the pandemic (7.13 ± 0.98% vs 7.18 ± 1.01%, P = 0.186). Teleworking (estimate 0.206, P = 0.004) and living with a dog (estimate −0.149, P = 0.038) were significantly associated with changes in HbA1c levels after adjusting for covariates. There was no significant difference in the proportion of patients who received treatment intensification for diabetes during the pandemic and before the pandemic in either the elderly or non‐elderly patients.ConclusionsOverall glycemic control did not worsen during the pandemic. Nonetheless, environmental factors, including telework, were found to influence glycemic control in patients with diabetes. Further studies are needed to clarify whether the COVID‐19 pandemic could affect treatment intensification for diabetes. 相似文献
49.
Haruhisa Kato Makiko Naito Tomoko Saito Takuto Hideyama Yasuhiro Suzuki Takashi Kimura Shin Kwak Hitoshi Aizawa 《JOURNAL OF CLINICAL NEUROLOGY》2022,18(4):463
Background and PurposeAmyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca2+ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS.MethodsSpecimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope.ResultsThis study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ2 test).ConclusionsIn sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism. 相似文献
50.
Hisato Shima Toshio Doi Takuya Okamoto Yusuke Higashiguchi Megumi Harada Tomoko Inoue Manabu Tashiro Seiichiro Wariishi Norimichi Takamatsu Kazuhiko Kawahara Kazuyoshi Okada Jun Minakuchi 《Internal medicine (Tokyo, Japan)》2022,61(12):1863
A 39-year-old woman was hospitalized for nephrotic syndrome. Laboratory test results showed increased serum creatinine levels and urinary excretions of beta-2-microglobulin, and N-acetyl-beta-D-glucosaminidase. A renal biopsy revealed collapsing focal segmental glomerulosclerosis (FSGS) and acute interstitial nephritis. Despite treatment with pulse steroid followed by oral high-dose glucocorticoids and cyclosporines, heavy proteinuria persisted. After low-density lipoprotein apheresis (LDL-A) therapy was initiated, her proteinuria gradually decreased, leading to complete remission. A repeat renal biopsy after treatment revealed no collapsing glomeruli. Immediate LDL-A should be performed to treat cases of collapsing FSGS poorly responding to other treatments. 相似文献