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   12064篇
  免费   777篇
  国内免费   7篇
  2024年   15篇
  2023年   38篇
  2022年   65篇
  2021年   232篇
  2020年   132篇
  2019年   205篇
  2018年   296篇
  2017年   244篇
  2016年   424篇
  2015年   617篇
  2014年   748篇
  2013年   800篇
  2012年   1071篇
  2011年   1050篇
  2010年   653篇
  2009年   501篇
  2008年   790篇
  2007年   679篇
  2006年   614篇
  2005年   562篇
  2004年   572篇
  2003年   454篇
  2002年   361篇
  2001年   355篇
  2000年   328篇
  1999年   227篇
  1998年   89篇
  1997年   77篇
  1996年   49篇
  1995年   48篇
  1994年   38篇
  1993年   29篇
  1992年   83篇
  1991年   54篇
  1990年   44篇
  1989年   48篇
  1988年   27篇
  1987年   28篇
  1986年   21篇
  1985年   23篇
  1984年   13篇
  1983年   15篇
  1982年   13篇
  1981年   12篇
  1980年   11篇
  1979年   9篇
  1978年   15篇
  1975年   13篇
  1974年   11篇
  1970年   6篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
941.
942.
Metabolic hormones, such as leptin, alter the input organization of hypothalamic circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by decreased food intake and adiposity. The gonadal steroid estradiol can also reduce appetite and adiposity, and it influences synaptic plasticity. Here we report that estradiol (E2) triggers a robust increase in the number of excitatory inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This rearrangement of synapses in the arcuate nucleus is leptin independent because it also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, and was paralleled by decreased food intake and body weight gain as well as increased energy expenditure. However, estrogen-induced decrease in body weight was dependent on Stat3 activation in the brain. These observations support the notion that synaptic plasticity of arcuate nucleus feeding circuits is an inherent element in body weight regulation and offer alternative approaches to reducing adiposity under conditions of failed leptin receptor signaling.  相似文献   
943.
Renal clearance of quantum dots   总被引:9,自引:0,他引:9  
The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.  相似文献   
944.
Previous studies have established that chlorpyrifos (CPS), fipronil, and nonane can all be metabolized by human liver microsomes (HLM) and a number of cytochrome P450 (CYP) isoforms. However, metabolic interactions between these three substrates have not been described. In this study the effect of either coincubation or preincubation of CPS with HLM or CYP isoforms with either fipronil or nonane as substrate was investigated. In both co- and preincubation experiments, CPS significantly inhibited the metabolism of fipronil or nonane by HLM although CPS inhibited the metabolism of fipronil more effectively than that of nonane. CPS significantly inhibited the metabolism of fipronil by CYP3A4 as well as the metabolism of nonane by CYP2B6. In both cases, preincubation with CPS caused greater inhibition than coincubation, suggesting that the inhibition is mechanism based.  相似文献   
945.
Mouse ficolin A is a plasma protein with lectin activity, and plays a role in host defense by binding carbohydrates, especially GlcNAc, on microorganisms. The ficolin A subunit consists of an N-terminal signal peptide, a collagen-like domain, and a C-terminal fibrinogen-like domain. In this study, we show that ficolin A can be synthesized and oligomerized in a cell and secreted into culture medium. We also identify a functionally relevant signal peptide of ficolin A by using MS/MS analysis to determine the N-terminal sequence of secreted ficolin A. When the signal peptide of mouse ficolin A was fused with enhanced green fluorescent protein (EGFP), EGFP was released into HEK 293 cell medium, suggesting that the signal peptide can efficiently direct ficolin A secretion. Moreover, our results suggest that the signal peptide of ficolin A has potential application for the production of useful secretory proteins.  相似文献   
946.
In this study, we describe a new approach to the production of naïve/synthetic human antibodies against the botulinum neurotoxin (BoNT). First, peptides that bind to BoNT serotype A (BoNT/A) were screened from a phage display of a combinatorial peptide library. One peptide, designated ANT 12-2 (TLPSPLALLTVH), was determined to interact with BoNT/A, as well as with other serotypes of BoNT. This peptide specifically reacted with the native form of BoNT/A, but not with its formalin-inactivated form. Next, a hybrid naïve/synthetic human Fab library was generated via the grafting of a peptide motif from ANT 12-2 into HCDR3 with randomized flanking residues. Through biopanning, the Fab clone, ANTHU-1, which harbors the HCDR3 sequence of VRIQRSPLALLSWGDV, was selected and confirmed in order to retain the same BoNT-binding characteristics as ANT 12-2.  相似文献   
947.
Bacterial lipopolysaccharide (LPS) is a potent stimulator of bone resorption in periodontitis. Co-culture systems of mouse calvaria-derived osteoblasts and bone marrow-derived preosteoclasts were used as an in vitro osteoclast differentiation. This study revealed that co-cultures using ddY or ICR mouse strain responded differently to LPS while responded equally to 1alpha,25(OH)2D3. Thus, the different response to LPS indicates dissimilarity of two mouse stains in their capacity for generating osteoclasts while the two mouse strains share the similarity in response to 1alpha,25(OH)2D3. To identify which cells between osteoblasts and preosteoclasts in the co-culture are responsible for the dissimilarity, the reciprocal co-cultures were performed between ddY and ICR mouse strains. The treatment of 1,25(OH)2D3 to ddY/ICR (osteoblasts from ddY/preosteoclasts from ICR) and ICR/ddY reciprocal co-cultures also showed the similarity. In case of LPS treatment, the results of ddY/ICR were similar to ddY/ddY and the results of the other reciprocal co-culture, ICR/ddY combination, were consistent with those of ICR/ICR. It suggests that the dissimilarity between the two mouse strains may resident in osteoblasts but not in preosteoclasts. Therefore, the osteoblast is responsible for mouse strain-dependent osteoclastogenesis in response to LPS. Although mouse models will continue to provide insights into molecular mechanisms of osteoclastogenesis, caution should be exercised when using different mouse strains, especially ddY and ICR strains as models for osteoclast differentiation.  相似文献   
948.
High cell density culturing has been conducted for the production of poly(3-hydroxybutyrate) fed-batch cultures ofRalstonia eutropha with phosphate limitation. It was found that a high glucose concentration inhibited the synthesis of P(3HB) in the high cell density culture ofR. eutropha. Although a low glucose concentration can trigger the synthesis of P(3HB) in a manner similar to that of phosphate limitation, it also limited both the P(3HB) synthesis and the cell growth, and led to a low P(3HB) productivity because glucose is the sole carbon source in this reaction. An unstructured model was proposed for predicting the cell growth and P(3HB) synthesis in high cell density cultures ofR. eutropha, where the phosphate concentration played a key role in the accumulation of P(3HB) and in cell growth. Good agreements were found between the experimental data and model predictions. The results of simulation showed that the final P(3HB) concentration would decrease more than 25% when the glucose was concentration increased to 40 g/L, and indicated that the optimal glucose concentration for P(3HB) production by high cell density cultures ofR. eutropha was around 9 g/L.  相似文献   
949.
The stabilization of optimum pH for cells can cause a higher erythropoietin (EPO) production rate and a good growth rate with the prolonged culture span in recombinant Chinese hamster ovary (r-CHO) cells. Our strategy for stabilizing the optimum pH in this study is to reduce the lactate production by adding sodium lactate to a culture medium. When 40 mM sodium lactate was added, a specific growth rate was decreased by approximately 22% as compared with the control culture. However the culture longevity was extended to 187 h, and more than a 2.7-fold increase in a final accumulated EPO concentration was obtained at 40 mM of sodium lactate. On the condition that caused the high production of EPO, a specific glucose consumption rate and lactate production rate decreased by 23.3 and 52%, respectively. Activity of lactate dehydrogenase (LDH) in r-CHO cells increased and catalyzed the oxidation of lactate to pyruvate, together with the reverse reaction, at the addition of 40 mM sodium lactate. The addition of 40 mM sodium lactate caused the positive effects on a cell growth and an EPO production in the absence of carbon dioxide gas as well as in the presence of carbon dioxide gas by reducing the accumulation of lactate.  相似文献   
950.
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