全文获取类型
收费全文 | 1007篇 |
免费 | 71篇 |
国内免费 | 1篇 |
专业分类
1079篇 |
出版年
2024年 | 2篇 |
2023年 | 12篇 |
2022年 | 10篇 |
2021年 | 24篇 |
2020年 | 20篇 |
2019年 | 17篇 |
2018年 | 36篇 |
2017年 | 26篇 |
2016年 | 27篇 |
2015年 | 69篇 |
2014年 | 60篇 |
2013年 | 75篇 |
2012年 | 96篇 |
2011年 | 83篇 |
2010年 | 61篇 |
2009年 | 43篇 |
2008年 | 67篇 |
2007年 | 67篇 |
2006年 | 47篇 |
2005年 | 43篇 |
2004年 | 39篇 |
2003年 | 37篇 |
2002年 | 22篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 8篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 9篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1958年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1079条查询结果,搜索用时 15 毫秒
111.
112.
113.
Hepatocyte growth factor installs a survival platform for colorectal cancer cell invasive growth and overcomes p38 MAPK-mediated apoptosis 总被引:1,自引:0,他引:1
Fassetta M D'Alessandro L Coltella N Di Renzo MF Rasola A 《Cellular signalling》2006,18(11):1967-1976
Hepatocyte growth factor (HGF) induces invasive growth, a biological program that confers tumor cells the capability to invade and metastasize by integrating cell proliferation, motility, morphogenesis, and survival. We here demonstrate that HGFR activation promotes survival of colorectal carcinoma (CRC) cells exposed to conditions that mimic those met during tumor progression, i.e. nutrient deprivation or substrate detachment, and following chemotherapeutic treatment. In all these conditions, a sustained activation of p38 MAPK delivers a main death signal that is overcome by cell treatment with HGF. HGF-driven survival requires the engagement of the PI3K/Akt/mTOR/p70S6K and ERK MAPK transduction pathways. Abrogation of p38 MAPK activity prevents CRC cell apoptosis also when these transduction pathways are inhibited, and treatment with HGF further increases survival. Engagement of these signaling cascades is also needed for HGF to induce CRC cell scattering, morphogenesis, motility and invasion. Activation of p38 MAPK signaling is therefore a main apoptotic switch for CRC cells in the stressful conditions encountered during tumor progression. Conversely, HGF orchestrates several biochemical pathways, which allow cell survival in these same conditions and promote the biological responses required for tumor invasive growth. Both p38 MAPK and HGF/HGFR signaling constitute potential molecular targets for inhibiting colorectal carcinogenesis. 相似文献
114.
115.
Bottai D Batoni G Esin S Florio W Brancatisano FL Favilli F Maisetta G Campa M 《Microbes and infection / Institut Pasteur》2006,8(8):2254-2261
The Mycobacterium tuberculosis TB8.4 (Rv1174c) gene encodes a secreted protein of 8.4 kDa (TB8.4) which has been suggested to be involved in reactivation of dormant mycobacteria. We have previously reported that inactivation of an identical gene (sa5k) in Mycobacterium bovis BCG causes impaired ability of the mutant strain (BCGsa5k::aph) to grow inside human macrophages. This study aimed to investigate the role of TB8.4 in the reactivation of aged cultures of BCG as well as the role of the sa5k gene in the resistance of BCG to intracellular stress conditions and adaptation to hypoxia. Although when added to aged cultures of BCG, TB8.4 caused a statistically significant increase in the number of colony-forming units, a similar effect was obtained in cultures incubated with BSA, suggesting a non-specific growth stimulation by TB8.4. Compared to parental BCG, the BCGsa5k::aph strain showed an increased susceptibility to reactive oxygen and nitrogen intermediates and to acid stress and an impaired ability to adapt to reduced O2 concentrations, when tested in the oxygen-limited Wayne culture system. These results suggest that the product of the sa5k gene (SA5K protein) has a role in both resistance of BCG to intracellular stress and in its adaptation to hypoxia. 相似文献
116.
To describe the differences in knee structure and non-knee structural factors between offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis and age- and sex-matched controls with no family history of knee osteoarthritis, a population-based longitudinal study of 163 matched pairs (mean age 45 years, range 26 to 61) was performed at baseline and about 2 years later. Knee cartilage defect score (0 to 4), cartilage volume and bone size were determined with T1-weighted fat saturation magnetic resonance imaging. Body mass index (BMI), lower-limb muscle strength, knee pain, physical work capacity at 170 beats/minute (PWC170) and radiographic osteoarthritis were measured by standard protocols. In comparison with controls, offspring had higher annual knee cartilage loss (-3.1% versus -2.0% at medial tibial site, -1.9% versus -1.1% at lateral tibial site and -4.7% versus -3.7% at patellar site, all P < 0.05), a greater increase in medial cartilage defect score (+0.15 versus -0.01, P < 0.05) and a greater decline in PWC170 (-0.7 watts/kg versus -0.4 watts/kg, P < 0.01). There were no significant differences in change in BMI, lower-limb muscle strength, knee pain or tibial bone area between these two groups; however, the differences in knee cartilage loss and cartilage defect change decreased in magnitude and became non-significant after adjustment for baseline cartilage volume, tibial bone area, BMI and knee pain. This longitudinal study suggests that knee cartilage loss, change in cartilage defects and decrease in physical fitness all have roles in the development of knee osteoarthritis, which is most probably polygenic but may reflect a shared environment. Importantly, the cartilage changes are largely dependent on baseline differences in cartilage volume, tibial bone area, BMI and knee pain, suggesting that these factors might have a role in their initiation. 相似文献
117.
The objective of this study was to describe the rate of change in knee cartilage volume over 4.5 years in subjects with symptomatic
knee osteoarthritis (OA) and to determine factors associated with cartilage loss. One hundred and five subjects were eligible
for this longitudinal study. Subjects' tibial cartilage volume was assessed by magnetic resonance imaging (MRI) at baseline,
at 2 years and at 4.5 years. Of 105 subjects, 78 (74%) completed the study. The annual percentage losses of medial and lateral
tibial cartilage over 4.5 years were 3.7 ± 4.7% (mean ± SD; 95% confidence interval 2.7 to 4.8%) and 4.4 ± 4.7% (mean ± SD;
95% confidence interval 3.4 to 5.5%), respectively. Cartilage volume in each individual seemed to track over the study period,
relative to other study participants. After multivariate adjustment, annual medial tibial cartilage loss was predicted by
lesser severity of baseline knee pain but was independent of age, body mass index and structural factors. No factors specified
a priori were associated with lateral cartilage volume rates of change. Tibial cartilage declines at an average rate of 4% per year
in subjects with symptomatic knee OA. There was evidence to support the concept that tracking occurs in OA. This may enable
the prediction of cartilage change in an individual. The only significant factor affecting the loss of medial tibial cartilage
was baseline knee pain, possibly through altered joint loading. 相似文献
118.
Lovisetto A Guzzo F Tadiello A Toffali K Favretto A Casadoro G 《Molecular biology and evolution》2012,29(1):409-419
Botanical fruits derive from ovaries and their most important function is to favor seed dispersal. Fleshy fruits do so by attracting frugivorous animals that disperse seeds together with their own excrements (endozoochory). Gymnosperms make seeds but have no ovaries to be transformed into fruits. Many species surround their seeds with fleshy structures and use endozoochory to disperse them. Such structures are functionally fruits and can derive from different anatomical parts. Ginkgo biloba and Taxus baccata fruit-like structures differ in their anatomical origin since the outer seed integument becomes fleshy in Ginkgo, whereas in Taxus, the fleshy aril is formed de novo. The ripening characteristics are different, with Ginkgo more rudimentary and Taxus more similar to angiosperm fruits. MADS-box genes are known to be necessary for the formation of flowers and fruits in Angiosperms but also for making both male and female reproductive structures in Gymnosperms. Here, a series of different MADS-box genes have been shown for the first time to be involved also in the formation of gymnosperm fruit-like structures. Apparently, the same gene types have been recruited in phylogenetically distant species to make fleshy structures that also have different anatomical origins. This finding indicates that the main molecular networks operating in the development of fleshy fruits have independently appeared in distantly related Gymnosperm taxa. Hence, the appearance of the seed habit and the accompanying necessity of seed dispersal has led to the invention of the fruit habit that thus seems to have appeared independently of the presence of flowers. 相似文献
119.
The EphA2 receptor plays key roles in many physiological and pathological events, including cancer. The process of receptor endocytosis and the consequent degradation have attracted attention as possible means of overcoming the negative outcomes of EphA2 in cancer cells and decreasing tumor malignancy. A recent study indicates that Sam (sterile alpha motif) domains of Odin, a member of the ANKS (ankyrin repeat and sterile alpha motif domain-containing) family of proteins, are important for the regulation of EphA2 endocytosis. Odin contains two tandem Sam domains (Odin-Sam1 and -Sam2). Herein, we report on the nuclear magnetic resonance (NMR) solution structure of Odin-Sam1; through a variety of assays (employing NMR, surface plasmon resonance, and isothermal titration calorimetry techniques), we clearly demonstrate that Odin-Sam1 binds to the Sam domain of EphA2 in the low micromolar range. NMR chemical shift perturbation experiments and molecular modeling studies point out that the two Sam domains interact with a head-to-tail topology characteristic of several Sam-Sam complexes. This binding mode is similar to that we have previously proposed for the association between the Sam domains of the lipid phosphatase Ship2 and EphA2. This work further validates structural elements relevant for the heterotypic Sam-Sam interactions of EphA2 and provides novel insights for the design of potential therapeutic compounds that can modulate receptor endocytosis. 相似文献
120.
de O S Mansur T Gonçalves FM Martins-Oliveira A Speciali JG Dach F Lacchini R Tanus-Santos JE 《Molecular and cellular biochemistry》2012,364(1-2):303-308
Molecular and Cellular Biochemistry - Migraine is a complex neurological disorder with a clear neurogenic inflammatory component apparently including enhanced nitric oxide (NO) formation. Excessive... 相似文献