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1.

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

Patients and Methods

We conducted a multicenter retrospective analysis in the Triveneto region of Italy.

Results

One hundred fifty-eight patients received radium 223 in our region. After a median follow-up of 9.5 months, 75 patients died. The median overall survival (OS) was 14.2 months, and the median progression-free survival (PFS) was 6.2 months. Seventy-one (45%) patients achieved progression as best response. Thirty-seven (23%) patients stopped the treatment early because of progression. Eastern Cooperative Oncology Group performance status was prognostic for OS (18.4 vs. 12.3 vs. 7.5 months; 0 vs. 1, P = .0062; 0 vs. 2, P = .0002), whereas previous prostatectomy or docetaxel exposure were not. A neutrophil to lymphocytes ratio ≥ 3 significantly impacted OS (18.1 vs. 9.7 months; P < .001) and slightly impacted PFS (6.6 vs. 5.6 months; P = .05). Patients with a baseline alkaline phosphatase (ALP) value ≥ 220 U/L had worse OS and PFS (24.1 vs. 10.5 months; 7.2 vs. 5.5 months; P < .001). Patients with changes in ALP value achieved better OS (P = .029) and PFS (P = .002). There was no difference according to the line of therapy (0 vs. ≥ 1; P = .490). The main grade 3/4 toxicities were anemia, asthenia, and thrombocytopenia.

Conclusion

This large real-world report confirms comparable OS and PFS data when compared with the pivotal study, as well as the predictive role of ALP and neutrophil to lymphocytes ratio. The definition of the optimal position of radium 223 in the treatment of metastatic castration-resistant prostate cancer has still to be defined.  相似文献   
2.
The prevalence of diagnosed diabetes among American Indians in New Mexico with varied genetic and cultural backgrounds is reported. Utilizing community-based registries, the prevalence in persons ages 35 years and older ranged from 9.8 percent among Jicarilla Apache Indians to 28.2 percent among Zuni Indians. All rates were significantly higher than the U.S. rate of 5.3 percent for the same age group. In addition, in three of the five tribal groups examined, the rates of diagnosed diabetes in Indians less than 35 years of age (range from 0.5 percent to 1.3 percent) were significantly higher than the U.S. rate of 0.4 percent for the same age group. The prevalence rates of diagnosed diabetes found in this study of American Indians in New Mexico were intermediate between those for the United States as a whole and the Pima Indians of southern Arizona. Reasons for the variations and the relative contribution of obesity, fitness, or genetic risk in the development of diabetes need further study.  相似文献   
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4.
In vitro comparisons of induction of perforin (PFP), granzyme B (GRB), production of cytokines, and cell-mediated cytotoxicity by interleukin-2 (IL-2), interleukin-15 (IL-15), or combinational IL-2/IL-15-induced lymphokine-activated killer cells were studied in this study. Whereas IL-2-induction was associated with a decrease in cultured cell population over a 7-day period, IL-15 alone or in combination with IL-2 resulted in significant increase including cytotoxic T lymphocytes and subsets of CD56+ lymphocytes, particularly cytokine-induced killer and cytolytic natural killer-T lymphocytes. The overall PFP, GRB, and tumor necrosis factor-alpha expression in different subtypes were also significantly higher with IL-15 alone or in combination with IL-2 induction with resultant superior cytotoxicity compared to IL-2 treatment. There was no significant advantage of addition of IL-2 over IL-15 induction. These results offer further information on the cytotoxic potency of these cytokines and their mechanisms of action implicating potential use of IL-15 as part of cytokine adoptive immunotherapy.  相似文献   
5.
This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.  相似文献   
6.
One hundred and forty-four patients with apparently benign gastric ulcer were endoscopically followed up in order to evaluate the outcome of the lesion. Particular attention was given to: (a) detect possible delay in diagnosing gastric cancer; (b) ascertain the frequency of association with epithelial dysplasia; (c) establish the role of markers, such as serum pepsinogen group I (PGI), and gastric juice CEA in predicting gastric ulcer evolution. Endoscopic and bioptic check-ups were carried out during the first year at 3, 6 and 12 months after endoscopic healing of the ulcer, and then at every symptomatic recurrence. Ten patients (6.9%) were found to present histological evidence of malignancy (within 3 months in six cases, between 6 and 12 months in three cases, and after 41 months in the rest). Four cases were early gastric cancers, and six had shown dysplastic changes of the mucosa at the edge or scar of the ulcer. Serum PGI levels were not significantly different in gastric cancer patients, while gastric juice CEA levels were sharply increased compared to those of gastric ulcer patients: nine out of ten patients had values above normal range. These data suggest that: (a) there may be some delay in diagnosing gastric carcinoma, and gastric ulcer patients should be controlled routinely more than once; (b) the presence of dysplasia indicates the need for prolonged follow-up, because of the high risk of association with or evolution into gastric cancer, and because of the higher number of early gastric cancer detections that this protocol allows; (c) further support in monitoring patients "at risk" may be afforded by gastric juice CEA determination.  相似文献   
7.
Journal of Public Health - Because an increasing number of patients travel internationally to seek medical care, Turkey offers comprehensive and outstanding services under extraordinary conditions...  相似文献   
8.
The aim of the present study was to examine subpreputial bacteriology and to compare it with the urine cultures of healthy male children. Seventy-two male children were divided into two groups as A and B according to age. In both groups preputial sac and urine cultures were taken simultaneously. Gram (+) enteric cocci were the most common isolated pathogens from the preputial sac in group B. Enterobacter, E. coli and staphylococci species were isolated from the urine cultures of three patients in group B. We could not find any difference between the preputial sac swabs of group A and B patients, but the isolation rate of urine cultures of group A patients was significantly higher than group B (p < 0.05). The findings of the present study support a potential role of the prepuce acting as a reservoir of faecal bacteria in the pathogenesis of UTI in male infants, especially in the first year of life. Improved penile hygiene after the first year of life does not alter the subpreputial bacteriology, but significantly decreases the contamination of urine. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
9.
NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases.  相似文献   
10.
A diversity of adhesive interactions occur between the cancer cell and host extracellular matrix which potentiate neoplastic expansion and metastatic dissemination. In miscellaneous malignant diseases, tumour progression has been observed to be associated with alterations in adhesion molecule expression. Recently, circulating soluble intercellular adhesion molecules have been identified. In this study, serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined in patients with gastric cancer. The study group consisted of 27 patients with previously untreated gastric adenocarcinoma. Four patients had stage II, two patients stage III and 21 patients stage IV disease according to the TNM classification. Nineteen patients had distant metastasis. The sera obtained from 18 healthy volunteers served as controls. Serum sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, we also studied other tumour-associated antigens, i.e. CEA and CA 19-9. Serum sICAM-1 levels were significantly increased in patients with gastric cancer (P < 0.0001). However, sE-selectin levels did not differ from the controls. sICAM-1 concentrations were also significantly higher in patients with distant metastasis and peritoneal spread (P = 0.0045 and P = 0.0157 respectively), whereas sE-Selectin levels were elevated only in patients with peritoneal metastasis (P = 0.033). Serum concentrations of sICAM-1 and sE-selectin correlated with CEA levels (P = 0.0013 and P = 0.003 respectively). Elevated levels of sE-selectin were associated with poorer prognosis (P = 0.0099), whereas sICAM-1 had no significant impact on survival. Our results suggest that increased sICAM-1 serum levels may reflect widespread disease and contribute directly to the progression of gastric cancer. Further investigation of the molecular mechanisms of adhesive tumour-host interactions may lead to a better understanding of the natural history of gastric cancer.  相似文献   
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