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91.
BACKGROUND: A number of studies have shown the importance of consumers' satisfaction toward pharmacy services. The measurement of patient satisfaction through different elements of services provided is challenging within the context of a dynamic economic environment. Patient satisfaction is the result of long-term established habits and expectations to the pharmacy as an institution. Few studies to date have attempted to discern whether these changes have led to increased patient satisfaction and loyalty, particularly within developing nations. OBJECTIVES: The objective of this study was to evaluate the elements of the services provided in Bulgarian pharmacies and their contribution to consumer satisfaction using a tetra-class model. Three main hypotheses were tested in pharmacies to validate the model in the case of complex services. Additionally, the contribution of the different service elements to the clients' satisfaction was studied. METHODS: The analysis was based on a survey of customers in central and district pharmacies in Sofia, Bulgaria. The data were analyzed through a correspondence analysis which was applied to the results of the 752 distributed questionnaires. RESULTS: It was observed that different dimensions of the pharmacies contribute uniquely to customer satisfaction, with consumer gender contributing greatly toward satisfaction, with type/location of pharmacy, consumer age, and educational degree also playing a part. The duration of time over which the consumers have been clients at a given pharmacy influences the subsequent service categorization. CONCLUSIONS: This research demonstrated that the tetra-class model is suitable for application in the pharmaceutical sector. The model results could be beneficial for both researchers and pharmacy managers.  相似文献   
92.
Bicyclic furano pyrimidine nucleosides have been found to be highly potent and selective inhibitors of varicella zoster virus (VZV). They are inactive against herpes simplex virus and have been known for several decades as (unwanted) synthetic by-products in the Pd-catalysed coupling of acetylenes to 5-iodo nucleosides. These fluorescent bicyclic nucleosides are now established as a new family of potent antivirals. They are unusual in that they exhibit complete specificity for VZV and require an alkyl (or alkylaryl) side-chain for biological activity. The latter requirement confers extremely high lipophilicities on these compounds, unknown amongst chemotherapeutic nucleosides, which may be of considerable importance in formulation, dosing and tissue distribution. The most potent compounds reported are p-alkylaryl compounds, with EC50 values below 1 nM versus VZV and selectivity index values of around 1,000,000. Here, we review the discovery, synthesis, characterization, antiviral profile, SAR, mechanism of action and development prospects for this new family of antivirals.  相似文献   
93.
Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer's disease for which a cure has not yet been found. Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases. In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease. Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation. The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer's disease will be discussed in this review.  相似文献   
94.
We have assessed whether adult human non-neoplastic astrocytes exhibit DNA synthesis in vitro, as measured using a double immunofluorescence technique to detect incorporation of 5-bromodeoxyuridine (BrdU) by nuclei of glial fibrillary acidic protein (GFAP)-containing cells. Dissociated cell cultures containing GFAP+ cells were established from surgically resected temporal lobe tissue from 3 young adult individuals operated upon to remove epileptogenic foci. In 5–18-day-old cultures from each of the 3 individuals, we observed GFAP+ cells whose nuclei had incorporated BrdU. BrdU nuclear staining was found in GFAP+ cells with either flat or process-bearing morphologies. The mean mitotic index for the GFAP+ cells was 6% (range 2–12%) as compared to a mean mitotic index of 29% for the GMK-7 glioma cell line. Our results do indicate that astrocytes derived from young adult donors, unlike such cells derived at autopsy from elderly adults, are capable of DNA synthesis in vitro, albeit to a markedly lesser extent than reported for fetal human astrocytes.  相似文献   
95.
The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig‐to‐nonhuman‐primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple‐xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.  相似文献   
96.
Spiral computed tomography (CT) contrast angiography is a promising imaging modality for the diagnosis of pulmonary embolism but the negative predictive value of this test remains controversial. We performed a multi-center prospective cohort study to determine the safety of relying on a negative spiral CT contrast angiography scan to exclude pulmonary embolism. Patients presenting to the Emergency Departments of three tertiary care institutions with clinically suspected pulmonary embolism were potentially eligible for the study. Patients underwent a clinical evaluation to categorize pretest probability into low, moderate, and high categories, and had D-dimer testing performed. Patients at low pretest probability with normal D-dimer were considered to have pulmonary embolism excluded. The remaining patients underwent spiral CT contrast angiography scan of the pulmonary arterial circulation and bilateral venous ultrasound of the proximal leg veins. Patients who were confirmed to have pulmonary embolism or deep vein thrombosis were treated with anticoagulant therapy. Patients in whom the diagnosis of pulmonary embolism was excluded did not receive anticoagulant therapy and were followed for a 3-month period for the development of venous thromboembolic complications. Eight hundred fifty-eight (858) patients were enrolled in this study. Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%). The remaining 489 were referred for spiral CT contrast angiography scan and ultrasound. Sixty-seven patients were confirmed to have pulmonary embolism and an additional 15 patients with negative CT scans had proximal deep vein thrombosis (DVT) on ultrasound for a total prevalence of venous thromboembolism of 82/489 (16.8%). Two of 409 patients who had pulmonary embolism excluded in the initial evaluation phase developed proximal venous thromboembolism (0.5%; 95% CI 0% to 1.8%) in the 3-month follow-up period. These findings suggest that the combination of a negative spiral CT contrast angiography scan and normal venous ultrasound imaging safely excludes the diagnosis of pulmonary embolism in the Emergency Department setting.  相似文献   
97.

Objective

Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI.

Methods

We performed a retrospective cohort study of hypertensive patients undergoing elective major vascular surgery to determine the association between the number of antihypertensive medications continued on the morning of surgery and AKI at 48 hours postoperatively.

Results

A total of 406 patients who had undergone suprainguinal vascular surgery were included, and 10.3% suffered postoperative AKI. In multivariable analysis, the number of antihypertensive medications taken on the morning of surgery was independently associated with AKI (P = .026). Compared with patients who took no medication, taking one medication (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.68-3.75) and taking two or more medications (aOR, 2.70; 95% CI, 1.13-6.44) were associated with a 1.6-fold and 2.7-fold increased risk of postoperative AKI, respectively. Other predictors of AKI were suprarenal surgery (aOR, 3.37; 95% CI, 1.53-7.44), age (aOR, 2.29 per 10 years; 95% CI, 1.40-3.74), length of surgery (aOR, 1.40 per 1 hour; 95% CI, 1.10-1.76), hemoglobin drop (aOR, 1.37 per 10 g/L; 95% CI, 1.10-1.74), and history of coronary artery disease (aOR, 2.33; 95% CI, 1.08-5.00).

Conclusions

In patients undergoing major vascular surgery who are treated with chronic antihypertensive therapy, the administration of antihypertensive drugs on the morning of surgery is independently associated with an increased risk of postoperative AKI. Further prospective studies are needed to confirm this finding.  相似文献   
98.
99.
Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

  相似文献   
100.
Rehabilitation professionals are currently using heart rate (HR) in order to assess the sincerity of effort in certain evaluations. It has been shown that a relation exists between HR and pain but no study has measured cardiac response during both clinical and experimental pain among a patient population using an intra-subject design. Thirty patients with low back pain (LBP) participated in this study including 16 men. Clinical pain was induced by applying a postero-anterior pressure (PA) on a painful lumbar segment for 15 and 30s in order to reproduce the patient's typical LBP at an intensity ranging between 50 and 70/100. Experimental pain was induced with a 15s thermal stimulus at a temperature which reproduced the same pain intensity as the 15s PA. For both reproduced clinical pain durations, we observed a rise in HR ranging between 8.5% and 12.67%. However, unlike men, women's cardiac response failed to show a constant rise in HR during the 30s PA. For all subjects, the rise in HR was much lower during the experimental pain condition (p<0.001), reaching only 5%. On the other hand, galvanic skin responses were significantly higher during the experimental pain condition (p<0.001). During this same condition, women also had a greater rise in galvanic skin responses than men (p=0.04). Finally, a significant correlation was found between both types of pain. These results suggest that pain induced during a clinical evaluation will produce a significant HR augmentation. However, heart rate variability analysis showed greater sympathetic cardiac regulation for men. The sex differences observed in this study call for caution when interpreting HR during pain assessment.  相似文献   
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