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81.
A longitudinal, four-year study (2004–2007) with a cohort of 139 older adults (majority women;71%) was conducted to examine the impact of community-based nutrition and physical activity programs on health outcome measures. Demographic and anthropometric data were collected and nutrition screening was performed. Blood pressure, serum cholesterol and glucose levels, and pulse rate were also measured. The blood pressure, both mean systolic and diastolic, 141(± 19.0)/79.3 ± 9.7 (2004) vs. 127.8 ± 10.9/73.8 ± 10.2 mm Hg (2007), were improved (p < 0.05) in women. There were also improvements (p < 0.05 in both men and women) in pulse rate between 2004 and 2007. There is no doubt that nutrition education and exercise programs together enhanced the overall health and well being of these older adults. However, our findings emphasize the need for further systematic study and for appropriate biometric assessments to evaluate the full impact of nutrition education and physical activity interventions in older adults.  相似文献   
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Objective

Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll‐like receptor 4 (TLR‐4). The objective of this study was to investigate the involvement of TLR‐4 activation in the development and progression of autoimmune destructive arthritis.

Methods

A naturally occurring TLR‐4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). Mice with collagen‐induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin‐1 receptor antagonist (IL‐1Ra) gene deficiency were treated with TLR‐4 antagonist. The clinical score for joint inflammation, histologic characteristics of arthritis, and local expression of IL‐1 in joints were evaluated after treatment.

Results

The TLR‐4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR‐4 ligands, while having no effect on these parameters by itself. Treatment of CIA using TLR‐4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti–type II collagen immunity crucial for this model. Treatment with TLR‐4 antagonist strongly reduced IL‐1β expression in articular chondrocytes and synovial tissue. Furthermore, such treatment inhibited IL‐1–mediated autoimmune arthritis in IL‐1Ra−/− mice and protected the mice against cartilage and bone pathology.

Conclusion

In the present study, we demonstrate for the first time that inhibition of TLR‐4 suppresses the severity of experimental arthritis and results in lower IL‐1 expression in arthritic joints. Our data suggest that TLR‐4 might be a novel target in the treatment of rheumatoid arthritis.
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Fine-needle aspiration biopsy (FNAB) of breast is a minimally invasive sampling procedure with a proven value in the initial evaluation of patients with palpable breast lesions. FNAB is a simple, cost-effective, and relatively nontraumatic procedure that has replaced open surgical biopsy in majority of academic institutions across the world. There are, however, inherent limitations in the ability of FNAB to reliably diagnose small percentage of cases that are difficult to diagnose by cytomorphology alone and require excisional biopsy. This shortcoming may be minimized if the morphology can be complemented by a reliable diagnostic adjunct. This retrospective study was designed to assess the added value of telomerase immunostain in interpretation of breast FNABs. Telomerase is a ribonucleoprotein enzyme that has been shown to be activated in different malignant tumors, including breast cancer. Immunocytochemical detection of this molecular marker on cytologic smears and cellblocks may be helpful for interpretation of FNAB specimens. In our retrospective study, we found that 56% of the malignant breast cases (28/50) showed positive telomerase immunostaining while only 4% of the negative cases (2/50) stained with telomerase (positive predictive value: 93%, negative predictive value: 69%). Expression of telomerase on highly suspicious breast fine-needle aspirations may upgrade the diagnosis to malignancy. However, a negative telomerase cannot exclude the possibility of carcinoma.  相似文献   
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The purpose of this study was to develop a new monolithic matrix system to completely deliver glipizide, a Biopharmaceutics Classification System (BCS) Class II drug in a zero order manner over an extended time period. Two approaches were examined using drug in formulations that contain swellable hydroxypropylmethylcellulose (HPMC) or erodible polyethylene oxide (PEO). The matrices were prepared by dry blending selected ratios of polymers and ingredients using direct compression technique. Dissolution was assessed using modified USP apparatus II. Glucotrol XL push-pull osmotic pump (PPOP) was used as the reference. The interrelationship between matrix hydration, erosion and textural properties were determined and analyzed under the dissolution test conditions. Linear and reproducible release similar to that of Glucotrol XL was achieved for optimized matrices (f2>50) independent of hydrodynamic conditions. The kinetics of drug delivery was directly related to the synchronization of swelling, erosion and fractional release. HPMC matrices showed a significantly greater degree of hydration and swelling and stronger texture property relative to PEO matrices. Results indicate that in the case of low dose/low soluble drug, total drug release in a zero order manner heavily depends on the synchronization of erosion and swelling fronts during the entire dissolution study.  相似文献   
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The main aim of this study was to investigate whether there is a relationship between menstrual cycle phase and exercise-induced bronchoconstriction (EIB) in female athletes with mild atopic asthma. Seven eumenorrheic subjects with regular 28-day menstrual cycles were exercised to volitional exhaustion on day 5 [mid-follicular (FOL)] and day 21 [mid-luteal (LUT)] of their menstrual cycle. Pulmonary function tests were conducted pre- and post-exercise. The maximal percentage decline in post-exercise forced expiratory volume in 1 s (FEV1) and forced expiratory flow from 25 to 75% of forced vital capacity (FEF25–75%) was significantly greater (P<0.05) on day 21 (mid-LUT phase) (−17.35±2.32 and −26.28±6.04%, respectively), when salivary progesterone concentration was highest, compared to day 5 (mid-FOL phase) (−12.81±3.35 and −17.23±8.20%, respectively), when salivary progesterone concentration was lowest. The deterioration in the severity of EIB during the mid-LUT phase was accompanied by worsening asthma symptoms and increased bronchodilator use. There was a negative correlation between the percent change in pre- to post-exercise FEV1 and salivary progesterone concentration. However, no such correlation was found between salivary estradiol and the percentage change in pre- to post-exercise FEV1. This study has shown for the first time that menstrual cycle phase is an important determinant of the severity of EIB in female athletes with mild atopic asthma. Female asthmatic athletes may need to adjust their training and competition schedules to their menstrual cycle and to consider the potential negative effects of the LUT phase of the menstrual cycle on exercise performance.  相似文献   
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Pathology is the study of human illness. Throughout centuries of scientific discoveries, pathologic examination of tissue samples has been the gold standard for diagnosis and pathologists have been involved in the elucidation of aetiology, assessment of the biology, clinicopathologic correlation and prediction of prognosis. The advances in science and technology and focused interest in breast cancer research have provided ample opportunities for pathologists to participate in better understanding of the basic fundamental cascade of events leading to tumorigenesis in breast cancer. They also partnered with their clinical colleagues and scientists to find more effective therapeutic options. This change has been possible with recognition of the fact that morphology alone may not be sufficient to tell the entire story of clinical behaviour of all breast cancer patients. In addition, the realization of heterogeneity of breast cancer and the differences in the expression of various biomarkers and the observed differences in response to therapy have resulted in extensive efforts to better define the characters of each breast cancer subtype. It is now generally agreed that breast cancer is not a single disease and not all patients with breast cancer can benefit from the same therapy. These changes have brought new challenges for pathologists. Pathologist are now required to not only provide diagnosis, but also study the precise molecular characterization of each individual breast cancer case and play a significant role in the treatment planning of breast cancer patients. This remarkable change in the role of the pathologist require his/her involvement in the modern taxonomy of this disease and to rise to the challenge of genomic medicine and molecular diagnostics, which are the fastest growing areas of medicine. Emphasis should also been placed to create a new morphomolecular pathology and train our young pathologist to expand beyond morphology and to embrace the power of molecular diagnostics, in order to be able to effectively practise in the era of precision medicine.  相似文献   
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