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   5400篇
  免费   426篇
  国内免费   270篇
  2023年   50篇
  2022年   123篇
  2021年   253篇
  2020年   175篇
  2019年   207篇
  2018年   188篇
  2017年   135篇
  2016年   211篇
  2015年   341篇
  2014年   384篇
  2013年   414篇
  2012年   504篇
  2011年   443篇
  2010年   270篇
  2009年   243篇
  2008年   267篇
  2007年   242篇
  2006年   189篇
  2005年   177篇
  2004年   167篇
  2003年   120篇
  2002年   108篇
  2001年   106篇
  2000年   93篇
  1999年   99篇
  1998年   40篇
  1997年   51篇
  1996年   41篇
  1995年   38篇
  1994年   29篇
  1993年   33篇
  1992年   41篇
  1991年   37篇
  1990年   46篇
  1989年   36篇
  1988年   23篇
  1987年   24篇
  1986年   13篇
  1985年   14篇
  1984年   10篇
  1983年   10篇
  1982年   9篇
  1981年   8篇
  1979年   14篇
  1978年   8篇
  1975年   5篇
  1973年   9篇
  1972年   6篇
  1971年   9篇
  1968年   5篇
排序方式: 共有6096条查询结果,搜索用时 250 毫秒
141.

Objective

The evidence on whether there is work stress related dysregulation of the hypothalamic-pituitary-adrenal axis is equivocal. This study assessed the relation between work stress and diurnal cortisol rhythm in a large-scale occupational cohort, the Whitehall II study.

Methods

Work stress was assessed in two ways, using the job-demand-control (JDC) and the effort-reward-imbalance (ERI) models. Salivary cortisol samples were collected six times over a normal day in 2002–2004. The cortisol awakening response (CAR) and diurnal cortisol decline (slope) were calculated.

Results

In this large occupational cohort (N = 2,126, mean age 57.1), modest differences in cortisol patterns were found for ERI models only, showing lower reward (β = −0.001, P-value = 0.04) and higher ERI (β = 0.002, P-value = 0.05) were related to a flatter slope in cortisol across the day. Meanwhile, moderate gender interactions were observed regarding CAR and JDC model.

Conclusions

We conclude that the associations of work stress with cortisol are modest, with associations apparent for ERI model rather than JDC model.  相似文献   
142.
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.  相似文献   
143.
Chung  H. H.  Kamar  C. K. A.  Lim  L. W. K.  Liao  Y.  Lam  T. T.  Chong  Y. L. 《Journal of Ichthyology》2020,60(1):90-98
Journal of Ichthyology - The Kottelat rasbora Rasbora hobelmani is a small ray-finned fish categorized under the genus Rasbora in the Cyprinidae family. In this study, the complete mitogenome...  相似文献   
144.
The length-weight relationships (LWRs) were studied for eight seagrass fish from Wenchang, China, using gill nets (150*1 m, mesh size 0.5 cm), including Gerres oblongus, Ambassis kopsii, Halichoeres nigrescens, Sillago aeolus, Yongeichthys criniger, Oxyurichthys tentacularis, Lethrinus haematopterus and Hypoatherina tsurugae, in November 2017, March and August 2018. Results suggest that mean LWR parameters b for these eight seagrass fish varied from 2.801 for L. haematopterus to 3.640 for A. kopsii, and r2 valued from .950 for L. haematopterus to 0.993 for H. nigrescens. This study will help us to better understand the ecological parameters these seagrass fish.  相似文献   
145.
146.
Terpinen-4-ol has high fumigating activity to stored-grain pests including Tribolium confusum. To understand the detoxification of terpinen-4-ol in insects, proteomic analysis was performed to identify related proteins and pathways in response to terpinen-4-ol fumigation in T. confusum. By using isobaric tags for relative and absolute quantitation (iTRAQ)-based strategy, 4,618 proteins were obtained from T. confusum adults in the present study. Comparative proteomic analysis showed that 148 proteins were upregulated and 137 proteins were downregulated in beetles under the LC50 of terpinen-4-ol treatment for 24 hr. According to functional classifications, differentially expressed proteins (DEPs) were enriched in xenobiotic metabolism pathways. In the detoxification pathway, the levels of 25 cytochrome P450s, 5 glutathione S-transferases, and 2 uridine diphosphate (UDP)-glucuronosyltransferases were changed, most of which were upregulated in T. confusum exposed to terpinen-4-ol. The results indicated that terpinen-4-ol was potentially metabolized and detoxified by enzymes like P450s in T. confusum.  相似文献   
147.
ABSTRACT

Chronotype reflects time of day preferences for performing daily activities. Previous research within Asian and European cohorts indicates evening chronotype is associated with elevated cardiometabolic risk. However, evidence is limited from population-based US cohorts, particularly among women in whom evening chronotype prevalence may become higher after middle-age, coinciding with life stages associated with higher cardiovascular disease (CVD) risk. This cross-sectional study evaluated associations of chronotype with overall cardiovascular health (CVH), health behaviors, and cardiometabolic risk factors among 506 women (mean age = 37 ± 16y, 62% racial/ethnic minority) in the American Heart Association (AHA)’s Go Red for Women Strategically-Focused Research Network cohort at Columbia University (New York City, NY, USA). Chronotype was assessed using the validated Morningness-Eveningness Questionnaire (MEQ) and categorized as “evening”, “intermediate”, and “morning” chronotypes. Health behaviors (diet, physical activity, and sleep) were assessed using validated questionnaires. Anthropometrics, clinical blood pressure, and blood biomarkers were assessed at the clinic visit. CVH was evaluated using the AHA Life’s Simple 7 (LS7) metrics; LS7 scores of 0–8 and 9–14 were considered indicative of poor and moderate-to-high CVH, respectively. Linear and logistic regression models adjusted for age, race/ethnicity, education, health insurance, and menopausal status were used to examine associations of MEQ scores and chronotype categories with overall CVH, clinical cardiometabolic risk factors, and health behaviors. Overall, 13% of women identified as evening chronotypes, while 55% and 32% reported being intermediate and morning types. In linear models, higher MEQ scores were associated with higher AHA LS7 scores (β(SE) = 0.02(0.01); p = .014), indicative of more favorable CVH, and with health behaviors not included in the LS7. Higher MEQ scores were also associated with lower Pittsburgh Sleep Quality Index, i.e. better sleep quality, (β(SE) = ?0.07(0.02), p < .0001), lower insomnia severity (β(SE) = ?0.14(0.01), p < .0001), shorter time to fall asleep (β(SE) = ?0.28(0.14), p = .044), and less sedentary time (β(SE) = ?0.11(0.03), p = .001). In logistic regression models, evening chronotype, compared to intermediate/morning type, was associated with higher odds of having poor CVH (OR(95%CI):2.41(1.20–4.85)), not meeting AHA diet (OR(95%CI):2.89(1.59–5.23)) and physical activity guidelines (OR(95%CI):1.78(1.03–3.07)), and having short sleep (OR(95%CI):2.15(1.24–3.73)) or insomnia (OR(95%CI):2.69(1.53–4.75)). The evening type compared to morning type was also associated with being a current smoker (OR(95%CI):2.14(1.02–4.52)) and having poor sleep quality (OR(95%CI:2.35(1.27–4.37)) and long sleep onset latency (OR(95%CI:1.89(1.00–3.56)). In our cohort of women, evening chronotype was related to poor CVH, likely driven by its influence on health behaviors. These findings, although warranting confirmation prospectively in other populations, suggest chronotype is an important factor to consider and possibly target when designing lifestyle interventions for CVD prevention.  相似文献   
148.
Breast cancer is a popularly diagnosed malignant tumor. Genomic profiling studies suggest that breast cancer is a disease with heterogeneity. Chemotherapy is one of the chief means to treat breast cancer, while its responses and clinical outcomes vary largely due to the conventional clinicopathological factors and inherent chemosensitivity of breast cancer. Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, our study established a multi-mRNA-based signature model and constructed a relative nomogram in predicting distant-recurrence-free survival for patients receiving surgery and following chemotherapy. We constructed a signature of eight mRNAs (IPCEF1, SYNDIG1, TIGIT, SPESP1, C2CD4A, CLCA2, RLN2, and CCL19) with the LASSO model, which was employed to separate subjects into groups with high- and low-risk scores. Obvious differences of distant-recurrence-free survival were found between these two groups. This eight-mRNA-based signature was independently associated with the prognosis and had better prognostic value than classical clinicopathologic factors according to multivariate Cox regression results. Receiver operating characteristic results demonstrated excellent performance in diagnosing 3-year distant-recurrence by the eight-mRNA signature. A nomogram that combined both the eight-mRNA-based signature and clinicopathological risk factors was constructed. Comparing with an ideal model, the nomograms worked well both in the training and validation sets. Through the results that the eight-mRNA signature effectively classified patients into low- and high-risk of distant recurrence, we concluded that this eight-mRNA-based signature played a promising predictive role in prognosis and could be clinically applied in breast cancer patients receiving adjuvant chemotherapy.  相似文献   
149.
Colorectal cancer is one of the most common and leading malignancies globally. Long noncoding RNAs (lncRNAs) function as potentially critical regulator in colorectal cancer. LINC01234, a novel lncRNA in tumor biology, regulates the progression of various tumors. However, the tumorigenic mechanism of LINC01234 in colorectal cancer is still unclear. This study was performed with the aim to prospectively investigate clinical significance, effect, and mechanism of lncRNA LINC01234 in colorectal cancer. First, we found that LINC01234, localized in the cytoplasm, was increased in both colorectal cancer cell lines and tissues. Subsequent functional assays suggested LINC01234 knockdown suppressed cell proliferation, migration, and invasion of colorectal cancer cells, while blocked cell cycle and induced cell apoptosis. Moreover, we identified that miR-1284 was target of LINC01234, we further demonstrated a negative correlation with LINC01234 in colorectal cancer tissues and cells. Furthermore, miR-1284 targeted and suppressed tumor necrosis factor receptor–associated factor 6 (TRAF6). Loss-of-function assay revealed that LINC01234 silencing suppressed colorectal cancer progression through inhibition of miR-1284. In vivo subcutaneous xenotransplanted tumor model indicated LINC01234 knockdown inhibited in vivo tumorigenic ability of colorectal cancer via downregulation of TRAF6. Collectively, this study clarified the biological significance of LINC01234/miR-1284/TRAF6 axis in colorectal cancer progression, providing insights into LINC01234 as novel potential therapeutic target for colorectal cancer therapeutic from bench to clinic.  相似文献   
150.
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