首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   8104篇
  免费   542篇
  国内免费   198篇
耳鼻咽喉   126篇
儿科学   109篇
妇产科学   156篇
基础医学   1414篇
口腔科学   119篇
临床医学   849篇
内科学   1464篇
皮肤病学   233篇
神经病学   470篇
特种医学   432篇
外科学   1000篇
综合类   73篇
一般理论   2篇
预防医学   370篇
眼科学   162篇
药学   736篇
中国医学   137篇
肿瘤学   992篇
  2023年   47篇
  2022年   148篇
  2021年   305篇
  2020年   140篇
  2019年   219篇
  2018年   270篇
  2017年   222篇
  2016年   302篇
  2015年   443篇
  2014年   464篇
  2013年   549篇
  2012年   742篇
  2011年   741篇
  2010年   467篇
  2009年   381篇
  2008年   531篇
  2007年   516篇
  2006年   407篇
  2005年   384篇
  2004年   292篇
  2003年   213篇
  2002年   192篇
  2001年   101篇
  2000年   98篇
  1999年   70篇
  1998年   64篇
  1997年   56篇
  1996年   54篇
  1995年   38篇
  1994年   41篇
  1993年   28篇
  1992年   20篇
  1991年   24篇
  1990年   33篇
  1989年   32篇
  1988年   39篇
  1987年   21篇
  1986年   11篇
  1985年   20篇
  1984年   7篇
  1983年   6篇
  1982年   8篇
  1981年   10篇
  1980年   10篇
  1977年   5篇
  1976年   8篇
  1975年   10篇
  1971年   4篇
  1958年   14篇
  1955年   4篇
排序方式: 共有8844条查询结果,搜索用时 15 毫秒
991.
Protein tyrosine kinases (PTK) are key enzymes of mammalian signal transduction. For the fidelity of signal transduction, each PTK phosphorylates only one or a few proteins on specific Tyr residues. Substrate specificity is thought to be mediated by PTK-substrate docking interactions and recognition of the phosphorylation site sequence by the kinase active site. However, a substrate-docking site has not been determined on any PTK. C-terminal Src kinase (Csk) is a PTK that specifically phosphorylates Src family kinases on a C-terminal Tyr. In this study, by sequence alignment and site-specific mutagenesis, we located a substrate-docking site on Csk. Mutations in the docking site disabled Csk to phosphorylate, regulate, and complex with Src but only moderately affected its general kinase activity. A peptide mimicking the docking site potently inhibited (IC50 = 21 microM) Csk phosphorylation of Src but only moderately inhibited (IC50 = 422 microM) its general kinase activity. Determination of the substrate-docking site provides the structural basis of substrate specificity in Csk and a model for understanding substrate specificity in other PTKs.  相似文献   
992.
Purpose  Uterine sarcoma is a rare malignancy with the worst prognosis of all uterine cancers. This study evaluated the prognostic factors and treatment outcomes of patients with this disease. Methods  A retrospective analysis was performed on 127 patients with histologically verified uterine sarcoma who were treated and followed at the Asan Medical Center (Seoul, Korea) from 1989 to 2007. Results  Histological analyses revealed that 37 patients had endometrial stromal sarcoma, 44 had malignant mixed mullerian tumors and 46 had leiomyosarcoma. Surgical stages, as defined by the International Federation of Gynecology and Obstetrics (FIGO) system, were I in 82 patients, II in 6 patients, III in 18 patients and IV in 19 patients. All patients underwent surgical treatment and 72 patients received adjuvant therapy. The 10-year disease-free survival (DFS) rate was 30% and the 10-year overall survival (OS) rate was 48%, with a mean follow-up time of 38 months (ranging from 1 to 212 months). Adjuvant radiation and chemotherapy had limited impact on the outcome of early-stage disease. However, patients with advanced-stage disease who received adjuvant chemotherapy had significantly longer OS times. A multivariate analysis revealed that FIGO stage (P = 0.025), depth of myometrial invasion (P = 0.004), and complete cytoreduction (P = 0.030) were significantly associated with DFS, while menopausal status (P = 0.044), FIGO stage (P = 0.016), depth of myometrial invasion (P = 0.029), and lymph-vascular space invasion (LVSI) (P = 0.020) were significantly associated with OS. Conclusions  This study suggests that complete cytoreduction is important and adjuvant chemotherapy can help achieve favorable prognoses in patients with advanced stage disease. However, postmenopausal status, advanced FIGO stage, deep myometrial invasion, and positive LVSI were associated with poor prognosis.  相似文献   
993.
BACKGROUND: The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. METHODS AND RESULTS: The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index > or =2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. CONCLUSIONS: Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations.  相似文献   
994.
995.
AIM: TO evaluate the efficacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospectively analyzed the colonoscopic findings before and after short term anti- tuberculosis treatment in 18 patients with nonspecific ulcers on the ileocecal area and compared them with 7 patients of confirmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS: Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short-term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the "suspicious tuberculous colitis group" showing healing of ulcers and erosions and another is the "suspicious inflammatory bowel disease group" showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the "suspicious tuberculous colitis group" were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the "suspicious inflammatory bowel disease group" were finally diagnosed as Crohn' s disease or nonspecific colonic ulcers during long-term follow up, CONCLUSION: Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecific ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis.  相似文献   
996.
BACKGROUND: This study assessed the effects of combination therapy with simvastatin and carvedilol on clinical outcome in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). METHODS AND RESULTS: The study retrospectively analyzed the data from 672 patients with LV dysfunction [LV ejection fraction (LVEF) <40%] complicated with AMI who underwent percutaneous coronary intervention (PCI). The patients were divided into 4 treatment groups: combination group (n=160), simvastatin only group (n=216), carvedilol only group (n=242), neither treatment group (n=54). At 6 months after PCI, the LVEF had improved most significantly in the combination group. During 1-year follow-up, cardiac death occurred most frequently in the neither treatment group compared with the other 3 groups (combination: 4%, simvastatin alone: 7%, carvedilol alone: 8%, neither: 17%, p<0.001 between neither treatment and other 3 groups). The results on major adverse cardiovascular events (MACE) showed that the combination of simvastatin and carvedilol was associated with a relative risk reduction of 53% (p<0.001), treatment with simvastatin alone with a relative risk reduction of 44% (p=0.001), and carvedilol alone with a relative risk reduction of 40% (p=0.003) compared with neither treatment. The independent predictors of 1-year MACE were neither treatment, elevated high sensitivity C-reactive protein (> or =0.5 mg/dl), and old age (>70 years). CONCLUSION: Combination therapy with simvastatin and carvedilol had a positive impact on the endpoints of cardiovascular death and MACE and seems to have an additive beneficial effect on these endpoints in patients with LV dysfunction complicated with AMI who underwent PCI.  相似文献   
997.
AIM: To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS: A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS: Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes' stage and lymph node metastasis. Nuclear staining was also observed in 24 (19.4%) of 124 samples and dosely associated with Dukes' stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.  相似文献   
998.
Kobayashi S  Ohnuma K  Uchiyama M  Iino K  Iwata S  Dang NH  Morimoto C 《Blood》2004,103(3):1002-1010
CD26 is a T-cell activation antigen that contains dipeptidyl peptidase IV activity and binds adenosine deaminase. Recent work showed that specialized membrane microdomains, also known as lipid rafts, play a key role in T-cell signaling. In this study, we investigate the role of CD26 in cord blood T-cell activation and signal transduction. We demonstrated that different expression levels of CD26 were observed between cord blood T cells (CBTCs) and peripheral blood T cells (PBTCs) and that CD26(+)CD45RA(+) CBTCs were different compared with CD26(+)CD45RA(+) PBTCs. Moreover, the comitogenic effect of CD26 was not as pronounced in CBTCs as in PBTCs. We also showed that CD26 cross-linking induced less phosphorylation of T-cell receptor-signaling molecules, lymphoid T-cell protein tyrosine kinase (Lck), zeta-associated protein 70 (ZAP-70), T-cell receptor zeta (TCRzeta), and linker for activator of T cells (LAT) in CBTCs than in PBTCs. Furthermore, CD26 molecules associated with CD45RA molecules outside lipid rafts in CBTCs. Our results suggest that strong physical linkage of CD26 with CD45RA outside lipid rafts may be responsible for the attenuation of T-cell activation signaling through CD26, which may be responsible for immature immune response and the low incidence of severe graft-versus-host disease in cord blood transplantation.  相似文献   
999.

Purpose:

To identify MRI biomarkers that could be used to follow disease progression and therapeutic efficacy in one individual muscle in patients with myotonic dystrophy type 1 (DM1).

Materials and Methods:

Lower limb MRI and maximal ankle dorsiflexor strength assessment, using a hand‐held dynamometer, were performed in 19 DM1 patients and 6 control subjects. The volume of residual muscle tissue of Tibialis Anterior (TA) muscle was chosen as an index for muscle atrophy, and the T2‐relaxation‐time of the residual muscle tissue was measured to evaluate edema‐like lesions. The fat‐to‐water ratio was assessed using three‐point Dixon images to quantify fat infiltration in the entire muscle.

Results:

The intra‐observer variability of MRI indices (~5.2% for the residual muscle tissue volume and 2.5% for the fat‐to‐water ratio) was lower than that of the dorsiflexor torque measurement (~11.5%). A high correlation (r = 0.91) was found between maximal ankle dorsiflexor strength and residual TA muscle tissue volume in DM1 patients. Increases in the fat‐to‐water ratio and T2‐relaxation‐time were associated with a decrease in maximal ankle dorsiflexor strength.

Conclusion:

MRI appears as a noninvasive method which can be used to follow disease progression and therapeutic efficacy. J. Magn. Reson. Imaging 2012;35:678‐685. © 2011 Wiley Periodicals, Inc.  相似文献   
1000.

Objective

To evaluate the effect of computer-aided detection (CAD) system on observer performance in the detection of malignant lung nodules on chest radiograph.

Materials and Methods

Two hundred chest radiographs (100 normal and 100 abnormal with malignant solitary lung nodules) were evaluated. With CT and histological confirmation serving as a reference, the mean nodule size was 15.4 mm (range, 7-20 mm). Five chest radiologists and five radiology residents independently interpreted both the original radiographs and CAD output images using the sequential testing method. The performances of the observers for the detection of malignant nodules with and without CAD were compared using the jackknife free-response receiver operating characteristic analysis.

Results

Fifty-nine nodules were detected by the CAD system with a false positive rate of 1.9 nodules per case. The detection of malignant lung nodules significantly increased from 0.90 to 0.92 for a group of observers, excluding one first-year resident (p = 0.04). When lowering the confidence score was not allowed, the average figure of merit also increased from 0.90 to 0.91 (p = 0.04) for all observers after a CAD review. On average, the sensitivities with and without CAD were 87% and 84%, respectively; the false positive rates per case with and without CAD were 0.19 and 0.17, respectively. The number of additional malignancies detected following true positive CAD marks ranged from zero to seven for the various observers.

Conclusion

The CAD system may help improve observer performance in detecting malignant lung nodules on chest radiographs and contribute to a decrease in missed lung cancer.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号