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81.
Marieke A Vollebergh Esther H Lips Petra M Nederlof Lodewyk FA Wessels Jelle Wesseling Marc J vd Vijver Elisabeth GE de Vries Harm van Tinteren Jos Jonkers Michael Hauptmann Sjoerd Rodenhuis Sabine C Linn 《Breast cancer research : BCR》2014,16(3):R47
Introduction
BRCA-mutated breast cancer cells lack the DNA-repair mechanism homologous recombination that is required for error-free DNA double-strand break (DSB) repair. Homologous recombination deficiency (HRD) may cause hypersensitivity to DNA DSB-inducing agents, such as bifunctional alkylating agents and platinum salts. HRD can be caused by BRCA mutations, and by other mechanisms. To identify HRD, studies have focused on triple-negative (TN) breast cancers as these resemble BRCA1-mutated breast cancer closely and might also share this hypersensitivity. However, ways to identify HRD in non-BRCA-mutated, estrogen receptor (ER)-positive breast cancers have remained elusive. The current study provides evidence that genomic patterns resembling BRCA1- or BRCA2-mutated breast cancers can identify breast cancer patients with TN as well as ER-positive, HER2-negative tumors that are sensitive to intensified, DSB-inducing chemotherapy.Methods
Array comparative genomic hybridization (aCGH) was used to classify breast cancers. Patients with tumors with similar aCGH patterns as BRCA1- and/or BRCA2-mutated breast cancers were defined as having a BRCA-likeCGH status, others as non-BCRA-likeCGH. Stage-III patients (n = 249) had participated in a randomized controlled trial of adjuvant high-dose (HD) cyclophosphamide-thiotepa-carboplatin (CTC) versus 5-fluorouracil-epirubicin-cyclophosphamide (FE90C) chemotherapy.Results
Among patients with BRCA-likeCGH tumors (81/249, 32%), a significant benefit of HD-CTC compared to FE90C was observed regarding overall survival (adjusted hazard ratio 0.19, 95% CI: 0.08 to 0.48) that was not seen for patients with non-BRCA-likeCGH tumors (adjusted hazard ratio 0.90, 95% CI: 0.53 to 1.54) (P = 0.004). Half of all BRCA-likeCGH tumors were ER-positive.Conclusions
Distinct aCGH patterns differentiated between HER2-negative patients with a markedly improved outcome after adjuvant treatment with an intensified DNA-DSB-inducing regimen (BRCA-likeCGH patients) and those without benefit (non-BRCA-likeCGH patients). 相似文献82.
Background
Body image (BI) is a multidimensional construct that includes perceptual, attitudinal, behavioural components, and feedback from other people''s perception of oneself. The feedback from others and the degree to which one accepts or rejects it can determine self evaluation and perception. Body weight perception is a strong determinant of nutritional habits and weight management among adolescents. One of the barriers to reducing rise in obesity prevalence could be its cultural acceptability in some developing countries.Objective
To explore the gender influences on perception of self- and opposite-sex body images (BI), perceived body weight and the actual body weight categories at which discrepancies occur among the perceived BIs in undergraduates.Methods
This was a survey of perceptual dimension of BI, perceived body weight and actual body weight carried out in 121 undergraduates aged 21–29years.Results
Discrepancies occurred between self-perceived BI and each of actual body weight (p= 0.00 at 0.00–0.02 confidence interval (CI)), perceived body weight (p= 0.01 at 0.000–0.02 CI) and self-ideal BI (p= 0.03 at 0.000–0.05 CI) of normal-weight males. Self-perceived BI and perceived body weight also differed in normal-weight females (p= 0.02 at 0.000–0.04 CI). Discrepancies (p= 0.02 at 0.00–0.04 CI) occurred between self-perceived BI and self-ideal BI, and between self-perceived BI and desired BI (p= 0.02 at 0.00–0.04 CI) in overweight females. Gender differences occurred for self-ideal BI (p= 0.00 at 0.00–0.02 CI), ideal image for the opposite sex (IBIOS) (p= 0.02 at 0.00–0.04 CI) and desired BI (p= 0.00 at 0.00–0.02 CI).Conclusion
Normal-weight males perceived their BI differently from their actual body weight, perceived body weight and self-ideal BI whereas normal-weight females perceived their BI differently from only their perceived body weight. Discrepancies occur between self-ideal BI and self-perceived BI, and between self-perceived BI and desired BI in overweight females. There are differential perceptions of self-ideal BI, IBIOS and desired BI between males and females. 相似文献83.
目的研究低温含血保护液微流量持续灌注对热缺血猪心的保护作用,探讨心脏移植中供心保护的有效方法。方法24只离体猪心随机分为实验组(n=12,热缺血10min,4℃含血保护液持续灌注8h)和对照组(n=12,热缺血10min,4℃保护液浸泡保存8h),进行原位心脏移植,分别监测心脏复跳及血流动力学情况:心率(HR)、平均动脉压(MAP)、心输出量(CO),心肌肌钙蛋白T(cTnT)、肌红蛋白(Mb)水平。结果实验组心脏复跳情况、血流动力学优于对照组;对照组心肌蛋白显著高于实验组(P〈0.05)。结论低温含血保护液微流量持续灌注对热缺血猪心的心功能以及心肌组织有较好的保护作用。 相似文献
84.
Knechten H Stephan C Mosthaf FA Jaeger H Carganico A Lutz T Schewe K Mayr C Wolf E Wellmann E Tappe A 《European journal of medical research》2011,16(3):93-100
Objective
We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.Methods
All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.Results
The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was''+263 cells/mm3 (IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm3 (IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.Conclusions
This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting. 相似文献85.
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89.
SCA6 is caused by moderate CAG expansion in the alpha1A-voltage- dependent calcium channel gene 总被引:1,自引:3,他引:1
Riess O; Schols L; Bottger H; Nolte D; Vieira-Saecker AM; Schimming C; Kreuz F; Macek M Jr; Krebsova A; Macek M Sen; Klockgether T; Zuhlke C; Laccone FA 《Human molecular genetics》1997,6(8):1289-1293
Recently, moderate (CAG)>20 repeat expansions in the alpha1A-voltage-
dependent calcium channel gene (CACNL1A4) have been identified in a
previously unmapped type of SCA which has been named SCA6. We investigated
the (CAG)n repeat length of the CACNL1A4 gene in 733 patients with sporadic
ataxia and in 46 German families with dominantly inherited SCA which do not
harbor the SCA1, SCA2, or MJD1/SCA3 mutation, respectively. The SCA6 (CAG)n
expansion was identified in 32 patients most frequently with late
manifestation of the disease. The (CAG)n stretch of the affected allele
varied between 22 and 28 trinucleotide units and is therefore the shortest
trinucleotide repeat expansion causing spinocerebellar ataxia. The (CAG)n
repeat length is inversely correlated with the age at onset. In 11 parental
transmissions of the expanded allele no repeat instability has been
observed. Repeat instability was also not found for the normal allele
investigating 431 meioses in the CEPH families. Analyzing 248 apparently
healthy octogenerians revealed one allele of 18 repeats which is the
longest normal CAG repeat in the CACNL1A4 gene reported. The SCA6 mutation
causes the disease in approximately 10% of autosomal dominant SCA in
Germany. Most importantly, the trinucleotide expansion was observed in four
ataxia patients without obvious family history of the disease which
necessitates a search for the SCA6 (CAG)n expansion even in sporadic
patients.
相似文献
90.
目的利用CRISPR/Cas9系统,敲除小鼠黑色素瘤细胞系的MATP基因,为MATP基因的功能研究奠定基础。方法利用http://crispr.mit.edu/网站,设计针对MATP的特异性引物,并将引物链接到pCAS9/gRNA1载体。将阳性载体转染小鼠黑色素瘤细胞系B16F10,利用无限稀释的方法获得转染后的单克隆细胞株。提取不同细胞株的基因组,通过测序的方法进一步筛选出发生MATP基因切割的细胞株,并利用Western-blot的方法验证MATP的表达情况。结果成功获得了3株MATP基因敲除的细胞株,Western-blot结果表明,该细胞株不表达MATP蛋白。结论利用pCAS9/gRNA1载体,可以实现B16F10细胞系MATP基因的敲除。 相似文献