全文获取类型
收费全文 | 2419篇 |
免费 | 38篇 |
国内免费 | 133篇 |
专业分类
系统科学 | 62篇 |
丛书文集 | 114篇 |
教育与普及 | 14篇 |
理论与方法论 | 5篇 |
现状及发展 | 329篇 |
综合类 | 2065篇 |
自然研究 | 1篇 |
出版年
2024年 | 3篇 |
2023年 | 10篇 |
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 21篇 |
2019年 | 15篇 |
2018年 | 12篇 |
2017年 | 20篇 |
2016年 | 23篇 |
2015年 | 49篇 |
2014年 | 102篇 |
2013年 | 79篇 |
2012年 | 110篇 |
2011年 | 122篇 |
2010年 | 91篇 |
2009年 | 248篇 |
2008年 | 283篇 |
2007年 | 204篇 |
2006年 | 172篇 |
2005年 | 152篇 |
2004年 | 112篇 |
2003年 | 115篇 |
2002年 | 107篇 |
2001年 | 73篇 |
2000年 | 77篇 |
1999年 | 48篇 |
1998年 | 45篇 |
1997年 | 31篇 |
1996年 | 44篇 |
1995年 | 21篇 |
1994年 | 37篇 |
1993年 | 26篇 |
1992年 | 18篇 |
1991年 | 20篇 |
1990年 | 20篇 |
1989年 | 25篇 |
1988年 | 14篇 |
1987年 | 8篇 |
1986年 | 4篇 |
1955年 | 1篇 |
排序方式: 共有2590条查询结果,搜索用时 171 毫秒
991.
Mitochondrial dysfunction and protein kinase C (PKC) activation are consistently found in diabetic cardiomyopathy but their
relationship remains unclear. This study identified mitochondrial aconitase as a downstream target of PKC activation using
immunoblotting and mass spectrometry, and then characterized phosphorylation-induced changes in its activity in hearts from
type 1 diabetic rats. PKCβ2 co-immunoprecipitated with phosphorylated aconitase from mitochondria isolated from diabetic hearts. Augmented phosphorylation
of mitochondrial aconitase in diabetic hearts was found to be associated with an increase in its reverse activity (isocitrate
to aconitate), while the rate of the forward activity was unchanged. Similar results were obtained on phosphorylation of mitochondrial
aconitase by PKCβ2 in vitro. These results demonstrate the regulation of mitochondrial aconitase activity by PKC-dependent phosphorylation. This may
influence the activity of the tricarboxylic acid cycle, and contribute to impaired mitochondrial function and energy metabolism
in diabetic hearts.
Received 31 October 2008; received after revision 17 December 2008; accepted 2 January 2009 相似文献
992.
993.
The bacterial LexA transcriptional repressor 总被引:2,自引:0,他引:2
Bacteria respond to DNA damage by mounting a coordinated cellular response, governed by the RecA and LexA proteins. In Escherichia coli, RecA stimulates cleavage of the LexA repressor, inducing more than 40 genes that comprise the SOS global regulatory network.
The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation. In some
well-characterised pathogens, induction of the SOS response modulates the evolution and dissemination of drug resistance,
as well as synthesis, secretion and dissemination of the virulence. In this review, we discuss the structure of LexA protein,
particularly with respect to distinct conformations that enable repression of SOS genes via specific DNA binding or repressor
cleavage during the response to DNA damage. These may provide new starting points in the battle against the emergence of bacterial
pathogens and the spread of drug resistance among them. 相似文献
994.
Cellular mechanisms regulating human melanogenesis 总被引:2,自引:0,他引:2
H. Y. Park M. Kosmadaki M. Yaar B. A. Gilchrest 《Cellular and molecular life sciences : CMLS》2009,66(9):1493-1506
995.
Cell-cell adhesion is a critical property of all multi-cellular organisms and its correct regulation is critical during development,
differentiation, tissue building and maintenance, and many immune responses. The multi-talin-like FERM domain containing protein,
FrmA, is required during starvation-induced multi-cellular development of Dictyostelium cells. Loss of FrmA leads to increased cell-cell adhesion and results in impaired multi-cellular development, slug migration
and fruiting bodies. Further, mixing experiments show that FrmA null cells are excluded from the apex of wild-type mounds,
to which cells that normally form the organising centre known as the tip sort. These data suggest a critical role for FrmA
in regulating cell-cell adhesion, multi-cellular development and, in particular, the formation of the organising centre known
as the tip.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 28 August 2008; received after revision 10 October 2008; accepted 21 October 2008 相似文献
996.
A. C. S. Souza S. Azoubel K. C. S. Queiroz M. P. Peppelenbosch C. V. Ferreira 《Cellular and molecular life sciences : CMLS》2009,66(7):1140-1153
Reversible tyrosine phosphorylation is a key posttranslational regulatory modification of proteins in all eukaryotic cells
in normal and pathological processes. Recently a pivotal janus-faced biological role of the low molecular weight protein tyrosine
phosphatase (LMWPTP) has become clear. On the one hand this enzyme is important in facilitating appropriate immune responses
towards infectious agents, on the other hand it mediates exaggerated inflammatory responses toward innocuous stimuli. The
evidence that LMWPTP plays a role in oncological processes has added a promising novel angle. In this review we shall focus
on the regulation of LMWPTP enzymatic activity of signaling pathways of different immunological cells, the relation between
genetic polymorphism of LMWPTP and predisposition to some type of inflammatory disorders and the contribution of this enzyme
to cancer cell onset, growth and migration. Therefore, the LMWPTP is an interesting target for pharmacological intervention,
thus modifying both inappropriate cellular immune responses and cancer cell aggressiveness.
Received 15 August 2008; received after revision 06 October 2008; accepted 14 October 2008 相似文献
997.
The continuing disappearance of “pure” Ca2+ buffers 总被引:1,自引:1,他引:0
B. Schwaller 《Cellular and molecular life sciences : CMLS》2009,66(2):275-300
Advances in the understanding of a class of Ca2+-binding proteins usually referred to as “Ca2+ buffers” are reported. Proteins historically embraced within this group include parvalbumins (α and β), calbindin-D9k, calbindin-D28k
and calretinin. Within the last few years a wealth of data has accumulated that allow a better understanding of the functions
of particular family members of the >240 identified EF-hand Ca2+-binding proteins encoded by the human genome. Studies often involving transgenic animal models have revealed that they exert
their specific functions within an intricate network consisting of many proteins and cellular mechanisms involved in Ca2+ signaling and Ca2+ homeostasis, and are thus an essential part of the Ca2+ homeostasome. Recent results indicate that calbindin-D28k, possibly also calretinin and oncomodulin, the mammalian β parvalbumin,
might have additional Ca2+ sensor functions, leaving parvalbumin and calbindin-D9k as the only “pure” Ca2+ buffers.
Received 10 September 2008; received after revision 15 October 2008; accepted 4 November 2008 相似文献
998.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated pore loop channels. HCN channels are unique among
vertebrate voltage-gated ion channels, in that they have a reverse voltage-dependence that leads to activation upon hyperpolarization.
In addition, voltage-dependent opening of these channels is directly regulated by the binding of cAMP. HCN channels are encoded
by four genes (HCN1–4) and are widely expressed throughout the heart and the central nervous system. The current flowing through
HCN channels, designated Ih or If, plays a key role in the control of cardiac and neuronal rhythmicity (“pacemaker current”). In addition, Ih contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration
and synaptic transmission. In this review we give an overview on structure, function and regulation of HCN channels. Particular
emphasis will be laid on the complex roles of these channels for neuronal function and cardiac rhythmicity.
Received 22 August 2008; received after revision 22 September 2008; accepted 24 September 2008 相似文献
999.
W. E. G. Müller M. Kasueske X. Wang H. C. Schröder Y. Wang D. Pisignano M. Wiens 《Cellular and molecular life sciences : CMLS》2009,66(3):537-552
Two classes of sponges (animal phylum Porifera) possess a siliceous skeleton which is composed of spicules. Studying the optical
fiber-mechanical properties of large spicules from hexactinellid sponges (> 5 cm) it was demonstrated that they are effective
light-collecting optical fibers. Here, we report that the demosponge Suberites domuncula is provided with a biosensor system composed of the (organic) light producing luciferase and the (inorganic) light transducing
silica spicules. The light transmission feature of these smaller spicules (200 μm) has been demonstrated and the ability of
sponge tissue to generate light has been proven. Screening for a luciferase gene in S. domuncula was successful; the recombinant luciferase was prepared and shown to be bioactive. The luciferase protein is abundantly present
in the close neighborhood of the spicules. The expression of the luciferase gene is under the control of light.
Received 14 August 2008; received after revision 09 November 2008; accepted 26 November 2008 相似文献
1000.
Q.-Q. Li X.-X. Cao J.-D. Xu Q. Chen W.-J. Wang F. Tang Z.-Q. Chen X.-P. Liu Z.-D. Xu 《Cellular and molecular life sciences : CMLS》2009,66(3):504-515
We previously reported that treatment with P-glycoprotein (P-gp) substrates promotes in vitro invasion in multidrug-resistant (MDR) breast cancer cells. This effect is initiated by the P-gp pump function and mediated
by interaction of P-gp with some unknown component(s). However, the underlying mechanism(s) remains poorly understood. Here
we confirm a novel physical interaction between P-gp and cellular prion protein (PrPc). Blocking P-gp activity or depletion of PrPc inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further facilitated the formation of P-gp/PrPc clusters residing in caveolar domains and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the integrity
of caveolae were required for the drug-induced invasion. In addition, the P-gp/PrPc complex also played an important role in anti-apoptotic activity of MCF7/Adr cells.These data provide new insights into the
mode by which MDR breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a role for P-gp/ PrPc interaction in this process.
Received 4 September 2008; received after revision 16 November 2008; accepted 18 November 2008 相似文献