首页 | 本学科首页   官方微博 | 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   19178篇
  免费   2515篇
  国内免费   663篇
  22356篇
  2024年   135篇
  2023年   678篇
  2022年   962篇
  2021年   1473篇
  2020年   1412篇
  2019年   2022篇
  2018年   1310篇
  2017年   905篇
  2016年   825篇
  2015年   997篇
  2014年   1547篇
  2013年   1861篇
  2012年   840篇
  2011年   986篇
  2010年   547篇
  2009年   697篇
  2008年   628篇
  2007年   642篇
  2006年   610篇
  2005年   505篇
  2004年   407篇
  2003年   364篇
  2002年   310篇
  2001年   189篇
  2000年   175篇
  1999年   154篇
  1998年   154篇
  1997年   108篇
  1996年   119篇
  1995年   111篇
  1994年   89篇
  1993年   86篇
  1992年   95篇
  1991年   70篇
  1990年   40篇
  1989年   39篇
  1988年   48篇
  1987年   42篇
  1986年   28篇
  1985年   40篇
  1984年   31篇
  1983年   8篇
  1982年   15篇
  1981年   9篇
  1980年   14篇
  1979年   10篇
  1978年   4篇
  1977年   4篇
  1976年   3篇
  1970年   2篇
排序方式: 共有10000条查询结果,搜索用时 7 毫秒
101.
102.
Cervical cancer is still an important cause of death in countries like Colombia. We aimed to determine whether socioeconomic status of residential address (SES) and type of health insurance affiliation (HIA) might be associated with cervical cancer survival among women in Bucaramanga, Colombia. All patients residing in the Bucaramanga Metropolitan Area diagnosed with invasive cervical cancer (ICD-0–3 codes C53.X) between 2008 and 2016 (n = 725) were identified through the population-based cancer registry, with 700 women having follow-up data for >5 years (date of study closure: Dec 31, 2021), yielding an overall 5-year survival estimate (95 % CI) of 56.4 % (52.7 – 60.0 %). KM estimates of 5-year overall survival were obtained to assess differences in cervical cancer survival by SES and HIA. Multivariable Cox-proportional hazards modeling was also conducted, including interaction effects between SES and HIA. Five-year overall survival was lower when comparing low vs. high SES (41.9 % vs 57.9 %, p < 0.0001) and subsidized vs. contributive HIA (45.1 % vs 63.0 %, p < 0.0001). Multivariable Cox modeling showed increased hazard ratios (HR) of death for low vs. high SES (HR = 1.78; 95 % CI = 1.18–2.70) and subsidized vs. contributive HIA (HR = 1.44; 95 % CI = 1.13–1.83). The greatest disparity in HR was among women of low SES affiliated to subsidized HIA (vs. contributive HIA and high SES) (HR=2.53; 95 % CI = 1.62–3.97). Despite Colombia’s universal healthcare system, important disparities in cervical cancer survival by health insurance affiliation and socioeconomic status remain.  相似文献   
103.
BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality.MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses.ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant.ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.  相似文献   
104.
BackgroundAn increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity.MethodsThe study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates.ResultsThe average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50–69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946–50 and that of 1956–60. The increase in incidence was seen in Māori and Pākehā/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006‐13 to 78% in 2014–20. Survival rates were lower in older patients, females, and Māori patients.ConclusionThis study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Māori and Pākehā/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.  相似文献   
105.
Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.  相似文献   
106.
Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to ‘austerity’, a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents. The ethanolic extract of Piper longum was found to have preferential cytotoxicity towards PANC-1 human pancreatic cancer cells in a nutrient-deprived medium (NDM). Further investigation led to the identification of pipernonaline ( 3 ) as the lead compound with the strongest anti-austerity activity, inducing cell death and inhibiting migration in a normal nutrient medium, as well as strongly inhibiting the Akt/mTOR/autophagy pathway. Therefore, pipernonaline ( 3 ) holds promise as a novel antiausterity agent for the treatment of pancreatic cancer.  相似文献   
107.
细胞核移植技术已被证明是研究发育中核质相互关系的非常重要的手段之一,电融合技术也是近十年发展起来的新型细胞融合技术。本实验运用这两项技术,进行了鼠、兔目间核质杂交实验,小鼠8-细胞核在激活的兔去核卵母细胞中,发生了染色体超前凝聚及核膨胀,融合卵移植到小鼠输卵管4.5天后,冲洗出,有5.4%的重构卵发育到囊胚期,通过染色体检查,囊胚细胞中均为小鼠染色体,其中一个囊胚为正常小鼠核型(2 n=40,XX)。通过本实验,我们认为:鼠兔远缘核质杂交胚胎的早期发育是可能的。  相似文献   
108.
Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan-cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.  相似文献   
109.
Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile.  相似文献   
110.
Genetically and phenotypically identical immune cell populations can be highly heterogenous in terms of their immune functions and protein secretion profiles. The microfluidic chip-based single-cell highly multiplexed secretome proteomics enables characterization of cellular heterogeneity of immune responses at different cellular and molecular layers. Increasing evidence has demonstrated that polyfunctional T cells that simultaneously produce 2+ proteins per cell at the single-cell level are key effector cells that contribute to the development of potent and durable cellular immunity against pathogens and cancers. The functional proteomic technology offers a wide spectrum of cellular function assessment and can uniquely define highly polyfunctional cell subsets with cytokine signatures from live individual cells. This high-dimensional single-cell analysis provides deep dissection into functional heterogeneity and helps identify predictive biomarkers and potential correlates that are crucial for immunotherapeutic product design optimization and personalized immunotherapy development to achieve better clinical outcomes.  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