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   5764篇
  免费   419篇
  国内免费   4篇
  2023年   21篇
  2022年   11篇
  2021年   79篇
  2020年   100篇
  2019年   114篇
  2018年   203篇
  2017年   160篇
  2016年   254篇
  2015年   394篇
  2014年   394篇
  2013年   442篇
  2012年   572篇
  2011年   512篇
  2010年   304篇
  2009年   276篇
  2008年   371篇
  2007年   379篇
  2006年   301篇
  2005年   264篇
  2004年   252篇
  2003年   236篇
  2002年   165篇
  2001年   94篇
  2000年   81篇
  1999年   66篇
  1998年   28篇
  1997年   25篇
  1996年   14篇
  1995年   15篇
  1994年   7篇
  1993年   5篇
  1992年   8篇
  1991年   7篇
  1990年   4篇
  1989年   4篇
  1988年   3篇
  1987年   3篇
  1986年   1篇
  1985年   2篇
  1984年   2篇
  1983年   2篇
  1982年   2篇
  1981年   1篇
  1980年   3篇
  1979年   1篇
  1976年   2篇
  1975年   1篇
  1971年   2篇
排序方式: 共有6187条查询结果,搜索用时 15 毫秒
1.
Autophagy is an important catabolic program to respond to a variety of cellular stresses by forming a double membrane vesicle, autophagosome. Autophagy plays key roles in various cellular functions. Accordingly, dysregulation of autophagy is closely associated with diseases such as diabetes, neurodegenerative diseases, cardiomyopathy, and cancer. In this sense, autophagy is emerging as an important therapeutic target for disease control. Among the autophagy machineries, PIK3C3/VPS34 complex functions as an autophagy-triggering kinase to recruit the subsequent autophagy protein machineries on the phagophore membrane. Accumulating evidence showing that inhibition of PIK3C3/VPS34 complex successfully inhibits autophagy makes the complex an attractive target for developing autophagy inhibitors. However, one concern about PIK3C3/VPS34 complex is that many different PIK3C3/VPS34 complexes have distinct cellular functions. In this study, we have developed an in vitro PIK3C3/VPS34 complex monitoring assay for autophagy inhibitor screening in a high-throughput assay format instead of targeting the catalytic activity of the PIK3C3/VPS34 complex, which shuts down all PIK3C3/VPS34 complexes. We performed in vitro reconstitution of an essential autophagy-promoting PIK3C3/VPS34 complex, Vps34–Beclin1–ATG14L complex, in a microwell plate (96-well format) and successfully monitored the complex formation in many different conditions. This PIK3C3/VPS34 complex protein assay would provide a reliable tool for the screening of autophagy-specific inhibitors.  相似文献   
2.
Semitransparent solar cells have attracted significant attention for practical applications, such as windows in buildings and automobiles. Here, semitransparent, highly efficient, 1D nanostructured perovskite solar cells are demonstrated employing anodized aluminum oxide (AAO) as a scaffold layer. The parallel nanopillars in the perovskite layer enable construction of haze‐free semitransparent devices without any hysteresis behavior. By controlling the pore size in the AAO, the volume occupied by the perovskite layer can be precisely varied, and the color neutrality of the resulting devices can be achieved. With the incorporation of a transparent cathodic electrode (indium tin oxide) with a buffer layer (MoOx), a highly efficient semitransparent nanopillared perovskite solar cell is achievable with a power‐conversion efficiency of 9.6% (7.5%) and a whole device average visible light transmittance of 33.4% (41.7%). To determine the role of the scaffold layer in improving the photoelectrical properties of the cell, impedance spectroscopy analyses are performed, revealing that the AAO‐structured perovskite layer suppresses internal ion diffusion and enables critical improvements in long‐term stability under continuous illumination.  相似文献   
3.
Mammalian polo-like kinase 1 (Plk1) has been studied intensively as a key regulator of various cell cycle events that are critical for proper M-phase progression. The polo-box domain (PBD) present in Plk1’s C-terminal non-catalytic region has been shown to play a central role in targeting the N-terminal kinase domain of Plk1 to specific subcellular locations. Subsequent studies reveal that PBD binds to a phosphorylated motif generated by one of the two mechanisms - self-priming by Plk1 itself or non-self-priming by a Pro-directed kinase, such as Cdc2. Here, we comparatively review the differences in the biochemical steps of these mechanisms and discuss their physiological significance. Considering the diverse functions of Plk1 during the cell cycle, a better understanding of how the catalytic activity of Plk1 functions in concert with its cis-acting PBD and how this coordinated process is intricately regulated to promote Plk1 functions will be important for providing new insights into different mechanisms underlying various Plk1-mediated biological events that occur at the multiple stages of the cell cycle.  相似文献   
4.
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.  相似文献   
5.

Objective

To analyze trends in the use of partial nephrectomy, we evaluated which individual factors of renal nephrometry score (RNS) influenced the operative approach bi-annually from 2008 to 2014.

Materials and Methods

We performed a retrospective review of renal cell carcinoma treated by surgery in 2008, 2010, 2012, and 2014. The complexity of renal masses was measured using the R.E.N.A.L. nephrometry scoring system with CT or MRI. Group comparison in terms of operation year and surgical type (partial nephrectomy versus radical nephrectomy) was performed. We developed a nomogram to quantitate the likelihood of selecting partial nephrectomy over radical nephrectomy.

Results

A total of 1106 cases (237 in 2008, 225 in 2010, 292 in 2012, and 352 in 2014) were available for the study. Over the study period, the proportion of partial nephrectomies performed increased steadily from 21.5% in 2008 to 66.5% in 2014 (p < 0.05). Furthermore, use of partial nephrectomy increased steadily in all RNS complexity groups (low, moderate, and high) (p < 0.05). In the analysis of individual components of RNS, values of the R and N components increased statistically by year in the partial nephrectomy group (p < 0.05). Average AUC was 0.920.

Conclusions

The proportion of partial nephrectomies performed sharply increased over the study period. Additionally, over the study period, more partial nephrectomies were performed for renal masses of larger size and closer to the collecting system and main renal vessels. A nomogram developed based on this recent data set provides significant predictive value for surgical decision making.  相似文献   
6.
There is evidence that telomere length (TL), telomerase activity (TA), and age are related to the replicative potential of human nucleus pulposus chondrocytes (NPCs). However, it has not yet been established if any of these factors can serve as predictors of the replicative potential of NPCs. To establish predictors of the replicative potential of NPCs, we evaluated potential relationships between replicative capacity of NPCs, initial TL (telomere length at the first passage), initial TA (telomerase activity at the first passage), and age. Nucleus pulposus specimens were obtained from 14 patients of various ages undergoing discectomy. NPCs were serially cultivated until the end of their replicative lifespans. Relationships among cumulative population doubling level (PDL), initial TL, initial TA, and age were analyzed. Initial TA was negatively correlated with age (r = -0.674, P = 0.008). However, no correlation between initial TL and age was observed. Cumulative PDL was also negatively correlated with age (r = -0.585, P = 0.028). Although the cumulative PDL appeared to increase with initial TL or initial TA, this trend was not statistically significant. In conclusion, age is the sole predictor of the replicative potential of human NPCs, and replicative potential decreases with age. Initial TL and initial TA are not predictors of replicative potential, and can serve only as reference values.  相似文献   
7.

Objective

Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).

Methods

Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.

Results

In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, p = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, p = 0.28).

Conclusion

Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.  相似文献   
8.
The seaweed genus Gracilaria is a potential candidate for the production of bioethanol due to its high carbohydrate content. Gracilaria is abundant throughout the world and can be found in both wild and cultivated forms. Differences in the ecological factors such as temperature, salinity, and light intensity affecting wild and cultivated specimens may influence the biochemical content of seaweeds, including the carbohydrate content. This study aimed to investigate the proximate composition and potential bioethanol production of wild and cultivated G. gigas and G. verrucosa. Bioethanol was produced using separate hydrolysis fermentation (SHF), employing a combination of enzymatic and acid hydrolysis, followed by fermentation with Saccharomyces cerevisiae ATCC 200062. The highest carbohydrate content was found in wild G. gigas. The highest galactose and glucose contents (20.21 ± 0.32 and 9.70 ± 0.49 g L?1, respectively), as well as the highest production of bioethanol (3.56 ± 0.02 g L?1), were also found in wild G. gigas. Thus, we conclude that wild G. gigas is the most promising candidate for bioethanol production. Further research is needed to optimize bioethanol production from wild G. gigas. Domestication of wild G. gigas is a promising challenge for aquaculture to avoid overexploitation of this wild seaweed resource.  相似文献   
9.
10.
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