全文获取类型
收费全文 | 959篇 |
免费 | 57篇 |
专业分类
1016篇 |
出版年
2024年 | 1篇 |
2023年 | 3篇 |
2022年 | 12篇 |
2021年 | 14篇 |
2020年 | 9篇 |
2019年 | 13篇 |
2018年 | 17篇 |
2017年 | 6篇 |
2016年 | 26篇 |
2015年 | 42篇 |
2014年 | 55篇 |
2013年 | 82篇 |
2012年 | 82篇 |
2011年 | 69篇 |
2010年 | 50篇 |
2009年 | 43篇 |
2008年 | 64篇 |
2007年 | 63篇 |
2006年 | 65篇 |
2005年 | 55篇 |
2004年 | 76篇 |
2003年 | 50篇 |
2002年 | 44篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1998年 | 8篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有1016条查询结果,搜索用时 15 毫秒
21.
Sun G Hagooly A Xu J Nyström AM Li Z Rossin R Moore DA Wooley KL Welch MJ 《Biomacromolecules》2008,9(7):1997-2006
The in vivo behavior of shell cross-linked knedel-like (SCK) nanoparticles is shown to be tunable via a straightforward and versatile process that advances SCKs as attractive nanoscale carriers in the field of nanomedicine. Tuning of the pharmacokinetics was accomplished by grafting varied numbers of methoxy-terminated poly(ethylene glycol) (mPEG) chains to the amphiphilic block copolymer precursors, together with chelators for the radioactive tracer and therapeutic agent (64)Cu, followed by self-assembly into block copolymer micelles and chemical cross-linking throughout the shell regions. (64)Cu-radiolabeling was then performed to evaluate the SCKs in vivo by means of biodistribution experiments and positron emission tomography (PET). It was found that the blood retention of PEGylated SCKs could be tuned, depending on the mPEG grafting density and the nanoparticle surface properties. A semiquantitative model of the density of mPEG surface coverage as a function of in vivo behavior was applied to enhance the understanding of this system. 相似文献
22.
23.
In vitro micropropagation by direct organogenesis and somatic embryogenesis via callus was developed for Crambe tataria (Brassicaceae). C. tataria is an endemic species of the Pontic-Pannonic region, but it is also present in Italy, where it is localized in Friuli on
a characteristic grassland formation, called “magredi”. C. tataria is regarded as an endangered species. Leaf and root explants were subjected to plant regulator treatments, which invoked
different morphogenic responses. Leaf explants produced more callus than root explants and a higher amount of callus was obtained
with 1 mg l−1 2,4-D in combination with 2 mg l−1 Kin. Somatic embryogenesis was obtained in calli maintained in a delayed subculture regime on media containing BAP in combination
with NAA. Root explants cultured with BAP combined with NAA developed adventitious rosette shoots. Shoots rooted on half-strength
MS media, and the number of roots per plantlet and their length were heavily dependent on sucrose content. The in vitro regenerated
plantlets were acclimatized ex vitro and a mean of 50% of the plantlets survived and showed a true-to-type growth habit. This
study describes the development of two in vitro micropropagation protocols, via direct organogenesis and via embryogenesis
from callus, that are the basis for the application of in vitro tools for the establishment of basal collections with representative
genetic diversity and for the long-term storage of plant genetic material. 相似文献
24.
Marcella Barbarino Daniele Cesari Maria Bottaro Luca Luzzi Asadoor Namagerdi Franca Maria Bertolino Cristiana Bellan Fabrizio Proietti Pasquale Somma Mariacarolina Micheli Maria Margherita de Santi Raffaella Guazzo Luciano Mutti Luigi Pirtoli Piero Paladini Paola Indovina Antonio Giordano 《Journal of cellular and molecular medicine》2020,24(10):5565-5577
Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs. 相似文献
25.
The metabolism of glucose 1-phosphate and glucose 6-phosphate and their influence on the metabolism of glucose in rat-diaphragm muscle 总被引:2,自引:4,他引:2 下载免费PDF全文
26.
27.
Filomena D’Amato Barbara Noli Laura Angioni Efisio Cossu Michela Incani Irene Messana Barbara Manconi Paola Solinas Raffaella Isola Stefano Mariotti Gian-Luca Ferri Cristina Cocco 《PloS one》2015,10(11)
To address the possible involvement of VGF peptides in obesity and diabetes, we studied type 2 diabetes (T2D) and obese patients, and high-fat diet induced obese mice. Two VGF peptides (NAPP-19 and QQET-30) were identified in human plasma by HPLC-ESI-MS. The VGF C-terminus, the above two cleaved peptides, and the TLQP-21 related peptide/s were studied using ELISA and immunohistochemistry. In euglycemic patients, plasma NAPPE and TLQP like peptides were significantly reduced with obesity (74±10 vs. 167±28, and 92±10 vs. 191±19 pmol/ml, mean+SEM, n = 10 and 6, obese vs. normal BMI, respectively, p<0.03). Upon a standard glucose load, a distinct response was shown for VGF C-terminus, TLQP and QQET-like (ERVW immunoreactive) peptides in euglycemic normal BMI patients, but was virtually abolished in euglycemic obese, and in T2D patients independently of BMI. High-fat diet induced obese mice showed reduced plasma VGF C-terminus, NAPPE and QQET-like (ERVW) peptide/s (3±0.2 vs. 4.6±0.3, 22±3.5 vs. 34±1.3, and 48±7 vs. 100±7 pmol/ml, mean+SEM, n = 8/group, obese vs. slim, respectively, p<0.03), with a loss of the response to glucose for all VGF peptides studied. In immunohistochemistry, TLQP and/or VGF C-terminus antibodies labelled VGF containing perikarya in mouse celiac ganglia, pancreatic islet cells and thin beaded nerve fibres in brown adipose tissues, with fewer in white adipose tissue. Upon the glucose load, tyrosine hydroxylase and VGF C-terminus immunoreactive axons became apparent in pancreatic islets of slim animals, but not in obese animals. Alltogether, a significant loss of VGF peptide immunoreactivity and/or their response to glucose was demonstrated in obese patients, with or without T2D, in parallel with a similar loss in high-fat diet induced obese mice. An involvement of VGF in metabolic regulations, including those of brown and/or white adipose tissues is underlined, and may point out specific VGF peptides as potential targets for diagnosis and/or treatment. 相似文献
28.
Nicla Contran Mariagrazia Tonelli Paolo Crosti Raffaella Cerana Massimo Malerba 《Acta Physiologiae Plantarum》2012,34(2):617-629
Reactive oxygen species (ROS) have pleiotropic effects in plants. ROS can lead to cellular damage and death or play key roles
in control and regulation of biological processes, such as programmed cell death (PCD). This dual role of ROS, as toxic or
signalling molecules, is possible because plant antioxidant system (AS) is able to achieve a tight control over ROS cellular
levels, balancing properly their production and scavenging. AS response in plant PCD has been clearly described only in the
hypersensitive response in incompatible plant–pathogen interactions and in the senescence process and has not been completely
unravelled. In sycamore (Acer pseudoplatanus L.) cultured cells PCD can be induced by Fusicoccin (Fc), Tunicamycin (Tu), and Brefeldin A (Ba). These chemicals induce
comparable PCD time course and extent, while H2O2 production is detectable only in Fc- and, to a lesser extent, in Ba-treated cells. In this paper the AS has been investigated
during PCD of sycamore cells, measuring the effects of the three inducers on the cellular levels of non-enzymatic and enzymatic
antioxidants. Results show that the AS behaviour is different in the PCD induced by the three chemicals. In Fc-treated cells
AS is mainly devoted to decrease the concentration of toxic intracellular H2O2 levels. On the contrary, in cells treated with Tu and Ba, the cell redox state is shifted to a more reduced state and the
enzymatic AS is partially down-regulated, allowing ROS to act as signalling molecules. 相似文献
29.
Vestibular inputs are constantly processed and integrated with signals from other sensory modalities, such as vision and touch. The multiply-connected nature of vestibular cortical anatomy led us to investigate whether vestibular signals could participate in a multi-way interaction with visual and somatosensory perception. We used signal detection methods to identify whether vestibular stimulation might interact with both visual and somatosensory events in a detection task. Participants were instructed to detect near-threshold somatosensory stimuli that were delivered to the left index finger in one half of experimental trials. A visual signal occurred close to the finger in half of the trials, independent of somatosensory stimuli. A novel Near infrared caloric vestibular stimulus (NirCVS) was used to artificially activate the vestibular organs. Sham stimulations were used to control for non-specific effects of NirCVS. We found that both visual and vestibular events increased somatosensory sensitivity. Critically, we found no evidence for supra-additive multisensory enhancement when both visual and vestibular signals were administered together: in fact, we found a trend towards sub-additive interaction. The results are compatible with a vestibular role in somatosensory gain regulation. 相似文献
30.
SHP-2 positively regulates myogenesis by coupling to the Rho GTPase signaling pathway 总被引:4,自引:0,他引:4 下载免费PDF全文
Kontaridis MI Eminaga S Fornaro M Zito CI Sordella R Settleman J Bennett AM 《Molecular and cellular biology》2004,24(12):5340-5352
Myogenesis is an intricate process that coordinately engages multiple intracellular signaling cascades. The Rho family GTPase RhoA is known to promote myogenesis, however, the mechanisms controlling its regulation in myoblasts have yet to be fully elucidated. We show here that the SH2-containing protein tyrosine phosphatase, SHP-2, functions as an early modulator of myogenesis by regulating RhoA. When MyoD was expressed in fibroblasts lacking functional SHP-2, muscle-specific gene activity was impaired and abolition of SHP-2 expression by RNA interference inhibited muscle differentiation. By using SHP-2 substrate-trapping mutants, we identified p190-B RhoGAP as a SHP-2 substrate. When dephosphorylated, p190-B RhoGAP has been shown to stimulate the activation of RhoA. During myogenesis, p190-B RhoGAP was tyrosyl dephosphorylated concomitant with the stimulation of SHP-2's phosphatase activity. Moreover, overexpression of a catalytically inactive mutant of SHP-2 inhibited p190-B RhoGAP tyrosyl dephosphorylation, RhoA activity, and myogenesis. These observations strongly suggest that SHP-2 dephosphorylates p190-B RhoGAP, leading to the activation of RhoA. Collectively, these data provide a mechanistic basis for RhoA activation in myoblasts and demonstrate that myogenesis is critically regulated by the actions of SHP-2 on the p190-B Rho GAP/RhoA pathway. 相似文献