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1.
Tympanic membranes (TM) that have healed spontaneously after perforation present abnormalities in their structural and mechanical properties; i.e., they are thickened and abnormally dense. These changes result in a deterioration of middle ear (ME) sound transmission, which is clinically presented as a conductive hearing loss (CHL). To fully understand the ME sound transmission under TM pathological conditions, we created a gerbil model with a controlled 50% pars tensa perforation, which was left to heal spontaneously for up to 4 weeks (TM perforations had fully sealed after 2 weeks). After the recovery period, the ME sound transmission, both in the forward and reverse directions, was directly measured with two-tone stimulation. Measurements were performed at the input, the ossicular chain, and output of the ME system, i.e., at the TM, umbo, and scala vestibuli (SV) next to the stapes. We found that variations in ME transmission in forward and reverse directions were not symmetric. In the forward direction, the ME pressure gain decreased in a frequency-dependent manner, with smaller loss (within 10 dB) at low frequencies and more dramatic loss at high frequency regions. The loss pattern was mainly from the less efficient acoustical to mechanical coupling between the TM and umbo, with little changes along the ossicular chain. In the reverse direction, the variations in these ears are relatively smaller. Our results provide detailed functional observations that explain CHL seen in clinical patients with abnormal TM, e.g., caused by otitis media, that have healed spontaneously after perforation or post-tympanoplasty, especially at high frequencies. In addition, our data demonstrate that changes in distortion product otoacoustic emissions (DPOAEs) result from altered ME transmission in both the forward and reverse direction by a reduction of the effective stimulus levels and less efficient transfer of DPs from the ME into the ear canal. This confirms that DPOAEs can be used to assess both the health of the cochlea and the middle ear.  相似文献   
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Serrated polyps (SPs) are precursors to one-third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early-onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy-based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early-onset polyps. Ninety-four thousand four hundred and twenty-seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High-risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high-grade dysplasia. We examined polyp prevalence with age and compared early- (age < 50) and late-onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty-five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High-risk SSLs were enriched in the ascending colon (44.1% vs 2.6-35.8% for other locations; P < .003). Early- and late-onset SPs had similar subsite distribution. Early-onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P < .001). Multiple conventional adenomas were more represented in late-onset groups (40.8% vs 33.8%, P < .001), with no difference in SSLs. The prevalence of conventional adenomas/high-risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high-risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early-onset than late-onset SSLs (62.9% vs 57.6%, P = .03). Conventional adenomas, SSLs, early- and late-onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC.  相似文献   
4.
Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.  相似文献   
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6.

Background

Glutamate plays a key role for post-ischaemic recovery of myocardial metabolism. According to post hoc analyses of the two GLUTAMICS trials, patients without diabetes benefit from glutamate with less myocardial dysfunction after coronary artery bypass surgery (CABG). Copeptin reflects activation of the Arginine Vasopressin system and is a reliable marker of heart failure but available studies in cardiac surgery are limited. We investigated whether glutamate infusion is associated with reduced postoperative rises of plasma Copeptin (p-Copeptin) after CABG.

Methods

A prespecified randomised double-blind substudy of GLUTAMICS II. Patients had left ventricular ejection fraction ≤0.30 or EuroSCORE II ≥3.0 and underwent CABG ± valve procedure. Intravenous infusion of 0.125 M L-glutamic acid or saline at 1.65 mL/kg/h was commenced 10–20 min before the release of the aortic cross-clamp and then continued for another 150 min P-Copeptin was measured preoperatively and postoperatively on day one (POD1) and day three. The primary endpoint was an increase in p-Copeptin from the preoperative level to POD1. Postoperative stroke ≤24 h and mortality ≤30 days were safety outcomes.

Results

We included 181 patients of whom 48% had diabetes. The incidence of postoperative mortality ≤30 days (0% vs. 2.1%; p = .50) and stroke ≤24 h (0% vs. 3.2%; p = .25) did not differ between the glutamate group and controls. P-Copeptin increased postoperatively with the highest values recorded on POD1 without significant inter-group differences. Among patients without diabetes, p-Copeptin did not differ preoperatively but postoperative rise from preoperative level to POD1 was significantly reduced in the glutamate group (73 ± 66 vs. 115 ± 102 pmol/L; p = .02). P-Copeptin was significantly lower in the Glutamate group on POD1 (p = .02) and POD 3 (p = .02).

Conclusions

Glutamate did not reduce rises of p-Copeptin significantly after moderate to high-risk CABG. However, glutamate was associated with reduced rises of p-Copeptin among patients without diabetes. These results agree with previous observations suggesting that glutamate mitigates myocardial dysfunction after CABG in patients without diabetes. Given the exploratory nature of these findings, they need to be confirmed in future studies.  相似文献   
7.
Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.  相似文献   
8.

Introduction

Left ventricular (LV) dysfunction is estimated to occur in 10%–25% of the general intensive care unit (ICU) population and is frequently seen as regional wall motion abnormalities (RWMAs). Although RWMA is mostly attributed to myocardial ischemia or infarction, some studies have suggested that nonischemic RWMA might also be prevalent. We sought to establish that RWMA can be seen in critically ill patients with normal coronary arteries and to explore reasons for RWMA in this population.

Methods

In this retrospective study, data from the hospital angiography register and the ICU register were collated between 2012 and 2019. Patients were identified who underwent angiography in conjunction with their ICU stay and had RWMA on echocardiography. Patients were divided into either those with non-obstructed or those with obstructed coronary arteries. Cardiac magnetic resonance imaging (cMRI) examinations were reviewed if they had been performed on patients with non-obstructed coronaries.

Results

We identified 53 patients with RWMA and non-obstructed coronary arteries and 204 patients with RWMA and obstructed coronary arteries. Patients with non-obstructed coronary arteries were more often female, younger, and had fewer cardiovascular risk factors. They less commonly had ST elevation, but more frequently had T-wave inversion or serious arrhythmias. Troponin levels were higher in patients with obstructed coronary arteries, but NT-proBNP was similar between the groups. There were no differences in risk-adjusted 90-day mortality between patients with non-obstructed versus obstructed coronary arteries (OR 1.21, [95% CI 0.56–2.64], p = .628). In those with non-obstructed coronary arteries, follow-up echocardiography was available for 38 patients, of whom 30 showed normalization of cardiac function. Of the 14 patients with non-obstructed coronary arteries on whom cMRI was performed, 7 had a tentative diagnosis of Takotsubo syndrome or myocardial stunning; 4 had a myocardial infarction (preexisting in 3 cases); 1 patient had acute myocarditis; 1 patient had post-myocarditis; and 1 patient was diagnosed with dilated cardiomyopathy.

Conclusion

RWMA can be seen to occur in critically ill patients in the absence of coronary artery obstruction. Several conditions can cause regional hypokinesia, and cMRI is useful to evaluate the underlying etiology.  相似文献   
9.
Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.  相似文献   
10.
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