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1.
Lim  Hui Fang  Tan  Nadia Suray  Dehghan  Roghayeh  Shen  Meixin  Liew  Mei Fong  Bee  Stella Wei Lee  Sia  Yee Yen  Liu  Jianjun  Khor  Chiea Chuen  Kwok  Immanuel  Ng  Lai Guan  Angeli  Veronique  Dorajoo  Rajkumar 《Lung》2022,200(3):401-407

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, PAdj?=?2.75?×?10?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

  相似文献   
2.
The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancer cell growth. Cytotoxicity MTT assays, clonogenic assays, and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin, and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer  相似文献   
3.
Repetition of jumps in dance and sport training poses a potential injury risk; however, non‐contact landing injuries are more common in athletes than dancers. This study aimed to compare the lower limb stiffness characteristics of dancers and athletes during drop landings to investigate possible mechanisms of impact‐related injuries. Kinematics and kinetics were recorded as 39 elite modern and ballet dancers (19 men and 20 women) and 40 college‐level team sport athletes (20 men and 20 women) performed single‐legged drop landings from a 30‐cm platform. Vertical leg stiffness and joint stiffness of the hip, knee, and ankle were calculated using a spring‐mass model. Stiffness data, joint kinematics, and moments were compared with a group‐by‐sex 2‐way analysis of variance. Multiple linear regression was used to assess the relative contribution of hip and knee and ankle joint stiffness to variance in overall vertical leg stiffness for dancers and athletes. Dancers had lower leg (P < 0.001), knee joint (P = 0.034), and ankle joint stiffness (P = 0.043) than athletes. This was facilitated by lower knee joint moments (P = 0.012) and greater knee (P = 0.029) and ankle joint (P = 0.048) range of motion in dancers. Males had higher leg (P < 0.001) and ankle joint stiffness (P < 0.001) than females. This occurred through lower ankle range of motion (P < 0.001) and greater ankle moment (P = 0.022) compared to females. Male and female dancers demonstrated reduced lower limb stiffness compared to athletes, indicating a more pliable landing technique. Dance training techniques could potentially inform approaches to injury prevention in athletes.  相似文献   
4.
BACKGROUND Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome(ACS)-related hospitalizations and post-revascularization is inadequate.AIM To evaluate the impact of gout on in-hospital outcomes of ACS hospitalizations,subsequent healthcare burden and predictors of post-revascularization inpatient mortality.METHODS We used the national inpatient sample(2010-2014) to identify the ACS and goutrelated hospitalizations, relevant comorbidities, revascularization and postrevascularization outcomes using the ICD-9 CM codes. A multivariable analysis was performed to evaluate the predictors of post-revascularization in-hospital mortality.RESULTS We identified 3144744 ACS-related hospitalizations, of which 105198(3.35%) also had gout. The ACS-gout cohort were more often older white males with a higher prevalence of comorbidities. Coronary artery bypass grafting was required more often in the ACS-gout cohort. Post-revascularization complications including cardiac(3.2% vs 2.9%), respiratory(3.5% vs 2.9%), and hemorrhage(3.1% vs 2.7%)were higher whereas all-cause mortality was lower(2.2% vs 3.0%) in the ACSgout cohort(P 0.001). An older age(OR 15.63, CI: 5.51-44.39), non-elective admissions(OR 2.00, CI: 1.44-2.79), lower household income(OR 1.44, CI: 1.17-1.78), and comorbid conditions predicted higher mortality in ACS-gout cohort undergoing revascularization(P 0.001). Odds of post-revascularization inhospital mortality were lower in Hispanics(OR 0.45, CI: 0.31-0.67) and Asians(OR 0.65, CI: 0.45-0.94) as compared to white(P 0.001). However, postoperative complications significantly raised mortality odds. Mean length of stay,transfer to other facilities, and hospital charges were higher in the ACS-gout cohort.CONCLUSION Although gout was not independently associated with an increased risk of postrevascularization in-hospital mortality in ACS, it did increase postrevascularization complications.  相似文献   
5.

Background

Persistent iatrogenic atrial septal defect (iASD) is a common but poorly characterized complication after cryoballoon (CB) pulmonary vein isolation (PVI) procedures. We therefore investigate its prevalence, evolution, risk factors, and clinical outcomes in a prospective longitudinal study.

Methods

A total of 108 patients (41 women, mean age 57 ± 11.3) underwent CB PVI for AF. Serial transesophageal echocardiography (TEE) was performed 9 months and then annually until 6 years after the procedure to study the characteristics of persistent iASD.

Results

Persistent iASD occurred in 33 (30.6%) patients 9 months after CB PVI. Spontaneous closure of iASD was found in 6 (22.2%) and 3 (15.8%) patients 2 and 3 years after the procedures, respectively. No spontaneous closure was observed on 4, 5, and 6-year TEE follow-up. The projected long-term persistence rate of iASD after CB PVI was therefore 20% (30.6% × 0.778 × 0.842). Using multivariate logistic regression, a higher number of cryoapplications (≥ 2 minutes) was the only independent predictor of persistent iASD 9 months after CB PVI (odds ratio [OR] 1.207; 95% confidence interval [CI], 1.033-1.411, P = 0.018). Two (1.9%) patients with significantly larger iASD size than the others (long diameter 12.6 ± 0.8 vs 3.7 ± 1.5 mm, P < 0.001; short diameter 10.9 ± 0.2 vs 3 ± 1.1 mm, P < 0.001) required percutaneous closure because of exertional dyspnea and right ventricular enlargement. Over 129.7 patient-years follow-up, during which iASD persisted, there was no occurrence of neurologic events.

Conclusions

Approximately one fifth of patients undergoing CB PVI will have permanently persistent iASD. Patients with defect sizes of greater than 10 mm may need percutaneous closure due to significant left-to-right shunting.  相似文献   
6.
7.
Clinical guidelines for the treatment of patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) recommend an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization. However, although patients with NSTEMI have a higher long‐term mortality risk than patients with ST‐segment elevation myocardial infarction (STEMI), they are often treated less aggressively; with those who have the highest ischemic risk often receiving the least aggressive treatment (the “treatment‐risk paradox”). Here, using evidence gathered from across the world, we examine some reasons behind the suboptimal treatment of patients with NSTEMI, and recommend approaches to address this issue in order to improve the standard of healthcare for this group of patients. The challenges for the treatment of patients with NSTEMI can be categorized into four “P” factors that contribute to poor clinical outcomes: patient characteristics being heterogeneous; physicians underestimating the high ischemic risk compared with bleeding risk; procedure availability; and policy within the healthcare system. To address these challenges, potential approaches include: developing guidelines and protocols that incorporate rigorous definitions of NSTEMI; risk assessment and integrated quality assessment measures; providing education to physicians on the management of long‐term cardiovascular risk in patients with NSTEMI; and making stents and antiplatelet therapies more accessible to patients.  相似文献   
8.
9.
BACKGROUNDChondrosarcoma, a cartilage matrix producing tumor, is the second most commonly observed primary bone tumor after osteosarcoma, accounting for 15% of all chest wall malignancies. We herein report the case of a patient with chondrosarcoma of the sternum and our management of the chest wall defects that presented following radical tumor resection.CASE SUMMARYA 31-year-old patient presented to our hospital with dull pain and a protruding mass overlying the chest for 3 mo. The presence of nocturnal pain and mass size progression was reported, as were overhead arm elevation-related limitations. Computed tomography showed a focal osteoblastic mass in the sternum with bony exostosis and adjacent soft tissue calcification. Positron emission tomography-computed tomography revealed hypermetabolic activity with a mass located over the upper sternum. Magnetic resonance imaging showed a focal ill-defined bony mass of the sternum with cortical destruction and periosteal reaction. Preoperative biopsy showed a consistent result with chondrosarcoma with immunohistochemical positivity for S100 and focal positivity for IDH-1. The grade II chondrosarcoma diagnosis was confirmed by postoperative pathology. The patient underwent radical tumor resection and chest wall reconstruction with a locking plate and cement spacer. The patient was discharged 1 wk after surgery without any complications. At the 1-year follow-up, there was no local recurrence on imaging. The functional scores, including Constant Score, Nottingham Clavicle Score, and Oxford Shoulder Score, showed the absence of pain in the performance of daily activities or substantial functional disabilities.CONCLUSIONThe diagnosis of chondrosarcoma must be considered when chest wall tumors are encountered. The surgical reconstructive materials, with a locking plate and cement spacer, used in our study are cost-effective and readily-available for the sternum defect.  相似文献   
10.
BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.  相似文献   
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