首页 | 官方网站   微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   51745篇
  免费   2532篇
  国内免费   405篇
医药卫生   54682篇
  2024年   49篇
  2023年   377篇
  2022年   938篇
  2021年   1750篇
  2020年   948篇
  2019年   1340篇
  2018年   1802篇
  2017年   1195篇
  2016年   1357篇
  2015年   1577篇
  2014年   2106篇
  2013年   2732篇
  2012年   4128篇
  2011年   4100篇
  2010年   2303篇
  2009年   2005篇
  2008年   3470篇
  2007年   3561篇
  2006年   3349篇
  2005年   3280篇
  2004年   2945篇
  2003年   2584篇
  2002年   2305篇
  2001年   341篇
  2000年   245篇
  1999年   346篇
  1998年   407篇
  1997年   354篇
  1996年   305篇
  1995年   306篇
  1994年   245篇
  1993年   183篇
  1992年   176篇
  1991年   132篇
  1990年   121篇
  1989年   111篇
  1988年   93篇
  1987年   73篇
  1986年   93篇
  1985年   86篇
  1984年   89篇
  1983年   82篇
  1982年   101篇
  1981年   77篇
  1980年   78篇
  1979年   52篇
  1978年   55篇
  1977年   44篇
  1976年   39篇
  1975年   35篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Objective

To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.

Design, setting, and participants

A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.

Outcome measurements and statistical analyses

Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.

Results and limitations

Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).

Conclusions

Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.

Patient summary

We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.  相似文献   
3.
OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition. METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders. Solubility test was performed based on ISO 7489. Flexural strength was determined by 3-point bending test based on ISO 4049. Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode. Both release measurements were performed for 15 d before and 15 d after recharging. Antibacterial test was conducted according to agar plate methods against S. mutans, by measuring the inhibition halos in 1-h and 15-d specimens. Data were analyzed by ANOVA. RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit. Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil. The control materials released no zinc. Vitremer with 10% ZnSO(4) released the highest amount of zinc. Fluoride release was similar for Ketac-Fil and Vitremer. In both cases, the highest amounts were released in the first 24 h. The growth inhibition halo of S. mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens. SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility.  相似文献   
4.
BACKGROUND: The activity and isoenzyme composition of N-acetyl-beta-D-hexosaminidase (EC.3.2.1.52) in seminal plasma of fertile and infertile men have been evaluated. However, no data are available on the isoenzyme content in seminal plasma from patients with secretory azoospermia. METHODS: The activity and isoenzyme composition of seminal plasma from 15 normozoospermic controls and 18 patients with secretory azoospermia were determined by fluorimetric methods. 4-Methylumbelliferil-2-acetamido-2-deoxy-beta-D-glucopyranoside and 4-methylumbelliferil-2-acetamido-2-deoxy-beta-D-glucopyranoside-6-sulfate were used as fluorigenic substrates. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency of the assays. RESULTS: No significant difference was found in total enzyme activity between the two groups, while isoenzyme A activity was significantly lower (p=0.004) and the ratio between total enzyme activity and isoenzyme A activity was significantly higher (p=0.04) in azoospermic patients compared to controls. The diagnostic efficiency of these evaluations was low (< or =75.7%). CONCLUSIONS: Our findings show that the isoenzyme composition of N-acetyl-beta-D-hexosaminidase in seminal plasma from patients with secretory azoospermia is significantly different from controls, but this difference does not represent a useful marker of secretory azoospermia. The fluorimetric assays are simple and rapid methods for evaluating the isoenzyme composition.  相似文献   
5.
6.
BACKGROUND: To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation. DESIGN: Prospective, observational study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENTS: Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation. METHODS: Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups. RESULTS: No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%). CONCLUSION: Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.  相似文献   
7.
BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.  相似文献   
8.
The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E2) levels (p < 0.001 and p < 0.05, respectively), FF E2 and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E2 levels.  相似文献   
9.
BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone.  相似文献   
10.
Female rats consistently show a pattern of differences in defensive behaviors compared to males which parallel the effects of exposure to a nonpainful threat stimulus (cat or cat odor) in the same tests and measures. These indications of greater defensiveness for females are particularly common in situations involving potential, as opposed to actual and present, threat, a factor which probably also reflects ceiling or floor effects in situations involving very intense defensiveness. In addition, pharmacological studies indicate sex differences in the effects of selective serotonin (5-HT) receptor agonists and antagonists on defensive responding. These findings indicate that sex effects must be considered in studies of the pharmacological control of defensive behaviors, and suggest that responsivity to sex effects may be an additional criterion for the suitability of animal models of anxiety.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号-23

京公网安备 11010802026262号