全文获取类型
收费全文 | 2125篇 |
免费 | 221篇 |
国内免费 | 10篇 |
专业分类
2356篇 |
出版年
2022年 | 27篇 |
2021年 | 33篇 |
2020年 | 25篇 |
2019年 | 47篇 |
2018年 | 43篇 |
2017年 | 54篇 |
2016年 | 58篇 |
2015年 | 87篇 |
2014年 | 91篇 |
2013年 | 126篇 |
2012年 | 118篇 |
2011年 | 135篇 |
2010年 | 99篇 |
2009年 | 85篇 |
2008年 | 98篇 |
2007年 | 107篇 |
2006年 | 108篇 |
2005年 | 98篇 |
2004年 | 86篇 |
2003年 | 65篇 |
2002年 | 74篇 |
2001年 | 62篇 |
2000年 | 64篇 |
1999年 | 49篇 |
1998年 | 24篇 |
1997年 | 17篇 |
1996年 | 14篇 |
1995年 | 19篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 46篇 |
1991年 | 30篇 |
1990年 | 27篇 |
1989年 | 34篇 |
1988年 | 25篇 |
1987年 | 19篇 |
1986年 | 18篇 |
1985年 | 26篇 |
1984年 | 16篇 |
1983年 | 18篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 8篇 |
1978年 | 15篇 |
1975年 | 10篇 |
1974年 | 12篇 |
1973年 | 17篇 |
1972年 | 11篇 |
1971年 | 7篇 |
1968年 | 8篇 |
排序方式: 共有2356条查询结果,搜索用时 15 毫秒
31.
A nuclear factor that enhances binding of thyroid hormone receptors to thyroid hormone response elements 总被引:24,自引:0,他引:24
Recent studies from this laboratory have demonstrated the presence of thyroid hormone response elements (TREs) in the 5'-flanking region of the rat alpha and TSH beta subunit genes. Using an avidin-biotin complex DNA binding assay, we have shown that these TREs bind the thyroid hormone (T3) receptor present in nuclear extracts of GH3 cells, as well as the in vitro synthesized Hc-erbA beta, which has been identified as a member of the family of T3 receptors. The binding of Hc-erbA beta to the alpha subunit TRE can be enhanced 3-4-fold by including GH3 nuclear extract in the binding assay. Binding to the TRE present in the TSH beta gene or the rat growth hormone gene was similarly enhanced, although to a lesser degree. The enhanced binding activity is trypsin-sensitive and heat labile, and is not reproduced by the addition of histones, bovine serum albumin, or cytosol instead of nuclear extract. Gel exclusion chromatography suggests a molecular size of approximately 65,000 Da. This protein, which is present in several different cell types, is also able to complement binding of the rat erbA alpha-1 and the pituitary-specific erbA beta-2 forms of the receptor. These data suggest that the binding of the T3 receptor to a TRE is augmented by another nuclear protein, which may be involved in the mechanism of action of thyroid hormone. 相似文献
32.
Somatic embryos in liquid culture can serve as a mass cloning system in a plant propagation program. A quantitative formulation of embryo development obtained from cell suspension cultures is used to develop a segregated kinetic model. The model is based on standard classification schemes as previously developed by plant physiologists. Dependent variables include carbohydrate concentrations (sucrose, fructose, and glucose) and biomass apportioned among the inoculum (free single cells, cell clusters), normal developmental stages, and aberrant cell and embryo types. Good agreement between the model and experimental results is indicated and allows for a rigorous approach to media optimization and reactor scaleup for embryo formation. 相似文献
33.
Abstract: Mouse brain tubulin was analyzed on isoelectric focusing gels. High-resolution gels utilizing Bio-Rad ampholytes (pH 4-6) revealed 5-6 bands in the region corresponding to the α-subunit of tubulin and 10 or more for the β-subunit. The same general banding pattern was observed regardless of the method of preparation of the tubulin. Two species prominent in the brains of immature mice, α6 and β2, virtually disappeared during maturation, while species β6 to β10 appeared. No significant changes from the mature pattern were seen during aging (examined at 12, 23, and 30 months of age). 相似文献
34.
35.
ChaoChien Chang KeeChin Sia JiaFeng Chang ChiaMo Lin ChuenMao Yang ITa Lee Thi Thuy Tien Vo KuoYang Huang WeiNing Lin 《Journal of cellular and molecular medicine》2022,26(14):3850
Obesity is a world‐wide problem, especially the child obesity, with the complication of various metabolic diseases. Child obesity can be developed as early as the age between 2 and 6. The expansion of fat mass in child age includes both hyperplasia and hypertrophy of adipose tissue, suggesting the importance of proliferation and adipogenesis of preadipocytes. The changed composition of gut microbiota is associated with obesity, revealing the roles of lipopolysaccharide (LPS) on manipulating adipose tissue development. Studies suggest that LPS enters the circulation and acts as a pro‐inflammatory regulator to facilitate pathologies. Nevertheless, the underlying mechanisms behind LPS‐modulated obesity are yet clearly elucidated. This study showed that LPS enhanced the expression of cyclooxygenase‐2 (COX‐2), an inflammatory regulator of obesity, in preadipocytes. Pretreating preadipocytes with the scavenger of reactive oxygen species (ROS) or the inhibitors of NADPH oxidase or p42/p44 MAPK markedly decreased LPS‐stimulated gene expression of COX‐2 together with the phosphorylation of p47phox and p42/p44 MAPK, separately. LPS activated p42/p44 MAPK via NADPH oxidase‐dependent ROS accumulation in preadipocytes. Reduction of intracellular ROS or attenuation of p42/p44 MAPK activation both reduced LPS‐mediated COX‐2 expression and preadipocyte proliferation. Moreover, LPS‐induced preadipocyte proliferation and adipogenesis were abolished by the inhibition of COX‐2 or PEG2 receptors. Taken together, our results suggested that LPS enhanced the proliferation and adipogenesis of preadipocytes via NADPH oxidase/ROS/p42/p44 MAPK‐dependent COX‐2 expression. 相似文献
36.
Sonic hedgehog signaling regulates Gli3 processing, mesenchymal proliferation, and differentiation during mouse lung organogenesis 总被引:4,自引:0,他引:4
Lack of Sonic hedgehog (Shh) signaling, mediated by the Gli proteins, leads to severe pulmonary hypoplasia. However, the precise role of Gli genes in lung development is not well established. We show Shh signaling prevents Gli3 proteolysis to generate its repressor forms (Gli3R) in the developing murine lung. In Shh(-/-) or cyclopamine-treated wild-type (WT) lung, we found that Gli3R level is elevated, and this upregulation appears to contribute to defects in proliferation and differentiation observed in the Shh(-/-) mesenchyme, where Gli3 is normally expressed. In agreement, we found Shh(-/-);Gli3(-/-) lungs exhibit enhanced growth potential. Vasculogenesis is also enhanced; in contrast, bronchial myogenesis remains absent in Shh(-/-);Gli3(-/-) compared with Shh(-/-) lungs. Genes upregulated in Shh(-/-);Gli3(-/-) relative to Shh(-/-) lung include Wnt2 and, surprisingly, Foxf1 whose expression has been reported to be Shh-dependent. Cyclins D1, D2, and D3 antibody labelings also reveal distinct expression patterns in the normal and mutant lungs. We found significant repression of Tbx2 and Tbx3, both linked to inhibition of cellular senescence, in Shh(-/-) and partial derepression in Shh(-/-); Gli3(-/-) lungs, while Tbx4 and Tbx5 expressions are less affected in the mutants. Our findings shed light on the role of Shh signaling on Gli3 processing in lung growth and differentiation by regulating several critical genes. 相似文献
37.
Achieving Molecular Selectivity in Imaging Using Multiphoton Raman Spectroscopy Techniques 总被引:2,自引:0,他引:2
Gary R. Holtom Brian D. Thrall Beek-Yoke Chin H. Steven Wiley Steven D. Colson 《Traffic (Copenhagen, Denmark)》2001,2(11):781-788
In the case of most optical imaging methods, contrast is generated either by physical properties of the sample (Differential Image Contrast, Phase Contrast), or by fluorescent labels that are localized to a particular protein or organelle. Standard Raman and infrared methods for obtaining images are based upon the intrinsic vibrational properties of molecules, and thus obviate the need for attached fluorophores. Unfortunately, they have significant limitations for live-cell imaging. However, an active Raman method, called Coherent Anti-Stokes Raman Scattering (CARS), is well suited for microscopy, and provides a new means for imaging specific molecules. Vibrational imaging techniques, such as CARS, avoid problems associated with photobleaching and photo-induced toxicity often associated with the use of fluorescent labels with live cells. Because the laser configuration needed to implement CARS technology is similar to that used in other multiphoton microscopy methods, such as two-photon fluorescence and harmonic generation, it is possible to combine imaging modalities, thus generating simultaneous CARS and fluorescence images. A particularly powerful aspect of CARS microscopy is its ability to selectively image deuterated compounds, thus allowing the visualization of molecules, such as lipids, that are chemically indistinguishable from the native species. 相似文献
38.
39.
Jing‐Yuan Chuang Wei‐Hung Yang Hsien‐Te Chen Chun‐Yin Huang Tzu‐Wei Tan Yuh‐Tzy Lin Chin‐Jung Hsu Yi‐Chin Fong Chih‐Hsin Tang 《Journal of cellular physiology》2009,220(2):418-426
CCL5 (previously called RANTES) is in the CC‐chemokine family and plays a crucial role in the migration and metastasis of human cancer cells. On the other hand, the effect of CCL5 is mediated via CCR receptor. RT‐PCR and flow cytometry studies demonstrated CCR5 but not CCR1 and CCR3 mRNA in oral cancer cell lines, especially higher in those with high invasiveness (SCC4) as compared with lower levels in HSC3 cells and SCC9 cells. Stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase‐9 (MMP‐9) production. MMP‐9 small interfering RNA inhibited the CCL5‐induced MMP‐9 expression and thereby significantly inhibited the CCL5‐induced cell migration. Activations of phospholipase C (PLC), protein kinase Cδ (PKCδ), and NF‐κB pathways after CCL5 treatment was demonstrated, and CCL5‐induced expression of MMP‐9 and migration activity was inhibited by the specific inhibitor of PLC, PKCδ, and NF‐κB cascades. In addition, migration‐prone sublines demonstrate that cells with increasing migration ability had more expression of MMP‐9, CCL5, and CCR5. Taken together, these results indicate that CCL5/CCR5 axis enhanced migration of oral cancer cells through the increase of MMP‐9 production. J. Cell. Physiol. 220: 418–426, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
40.
Inhibition of mutation and combating the evolution of antibiotic resistance 总被引:1,自引:0,他引:1 下载免费PDF全文
The emergence of drug-resistant bacteria poses a serious threat to human health. In the case of several antibiotics, including those of the quinolone and rifamycin classes, bacteria rapidly acquire resistance through mutation of chromosomal genes during therapy. In this work, we show that preventing induction of the SOS response by interfering with the activity of the protease LexA renders pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results in the derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce resistance-conferring mutations. Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance. 相似文献