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741.
742.
Stem cell therapy in stroke 总被引:2,自引:1,他引:1
Locatelli F Bersano A Ballabio E Lanfranconi S Papadimitriou D Strazzer S Bresolin N Comi GP Corti S 《Cellular and molecular life sciences : CMLS》2009,66(5):757-772
Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies
showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration
after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types.
In models of stroke, the principal mechanism by which any improvement has been observed, has been attributed to the release
of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and
angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however,
issues still need to be addressed for use in human subjects.
Received 23 June 2008; received after revision 24 September 2008; accepted 30 September 2008 相似文献
743.
C. Gordon-Thomson A. Kumari L. Tomkins P. Holford J. T. Djordjevic L. C. Wright T. C. Sorrell G. P. M. Moore 《Cellular and molecular life sciences : CMLS》2009,66(6):1116-1125
Chitotriosidase secreted by activated human macrophages has been implicated in the defence against chitin-bearing pathogens.
The antifungal properties of human chitotriosidase were investigated here following retroviral vector-mediated gene transfer
of the open reading frame of the chitotriosidase gene into Chinese hamster ovary cells. A chitinase assay confirmed that the
engineered cells secreted recombinant chitotriosidase constitutively. Two dimensional gel electrophoresis and western blotting
indicated that the recombinant protein is the major, chitin-binding, fifty kilodalton isoform. Culture medium conditioned
by the transduced cells inhibited growth of isolates of Aspergillus niger, Candida albicans and Cryptococcus neoformans. Furthermore, longevity was significantly increased in a mouse model of cryptococcosis when cells transduced with the chitotriosidase
gene and encapsulated in alginate microspheres were implanted subcutaneously in the animals. Engraftment of microcapsules
containing cells transduced with the chitotriosidase gene has the potential to combat infections caused by chitinous pathogens
through the prolonged delivery of recombinant chitotriosidase.
Received 29 November 2008; received after revision 11 January 2009; accepted 13 January 2009 相似文献
744.
745.
Sepsis is a common and serious medical condition caused by hemorrhage, trauma, or abdominal surgery. Despite new understanding
and much progress in therapies that specifically interfere with an interesting target, sepsis remains the leading causes of
death in critically ill patients. Various therapies have been studied, but the majority of these treatments fail in clinical
trials. It is clear that all septic patients exhibit coagulation abnormalities. These abnormalities range from subtle to marked
activation of coagulation system, and finally to fulminant DIC. Studies confirmed that carbon monoxide has important cytoprotective
function and anti-inflammatory properties. Until now, the question of whether CO plays a critical role in improving the coagulation
system and then decreasing mortality during sepsis has not yet been definitely answered. Attempts to confirm this strategy
may lead to new directions in the study of treatment of sepsis and the development of a novel agent for this disorder.
Received 13 August 2008; received after revision 29 October 2008; accepted 17 November 2008 相似文献
746.
747.
Differential insult-dependent recruitment of the intrinsic mitochondrial pathway during neuronal programmed cell death 总被引:1,自引:1,他引:0
Diwakarla S Nagley P Hughes ML Chen B Beart PM 《Cellular and molecular life sciences : CMLS》2009,66(1):156-172
Programmed cell death contributes to neurological diseases and may involve mitochondrial dysfunction with redistribution of
apoptogenic proteins. We examined neuronal death to elucidate whether the intrinsic mitochondrial pathway and the crosstalk
between caspase-dependent/-independent injury was differentially recruited by stressors implicated in neurodegeneration. After
exposure of cultured cerebellar granule cells to various insults, the progression of injury was correlated with mitochondrial
involvement, including the redistribution of intermembrane space (IMS) proteins, and patterns of protease activation. Injury
occurred across a continuum from Bax- and caspase-dependent (trophic- factor withdrawal) to Bax-independent, calpain-dependent
(excitotoxicity) injury. Trophic-factor withdrawal produced classical recruitment of the intrinsic pathway with activation
of caspase-3 and redistribution of cytochrome c, whereas excitotoxicity induced early redistribution of AIF and HtrA2/Omi,
elevation of intracellular calcium and mitochondrial depolarization. Patterns of engagement of neuronal programmed cell death
and the redistribution of mitochondrial IMS proteins were canonical, reflecting differential insult-dependencies.
Received 14 August 2008; received after revision 02 October 2008; accepted 23 October 2008 相似文献
748.
E. Sick N. Niederhoffer K. Takeda Y. Landry J.-P. Gies 《Cellular and molecular life sciences : CMLS》2009,66(7):1271-1282
Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcɛRI pathway, while only serosal mast
cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells. 4N1K,
a peptide agonist of CD47, rapidly caused exocytosis. Such exocytosis required increased intracellular calcium and was inhibited
by pertussis toxin and an antibody against the βγ dimer of a Gi protein. Cooperation with integrins and glycosylphosphatidylinositol-anchored proteins was necessary, since anti-integrin
antibodies and pretreatment with phosphatidylinositol-phospholipase C reduced exocytosis. Depletion of membrane cholesterol
inhibited exocytosis and decreased CD47 in lipid rafts, consistent with a CD47/integrin/Gi protein complex being located in rafts. An anti-CD47 antibody inhibited exocytosis induced by 4N1K and by mastoparan and
spermine, suggesting that basic secretagogues might target CD47. We propose that 4N1K-stimulated mast cell exocytosis involves
a CD47/integrin/Gi protein complex.
Received 8 December 2008; received after revision 12 January 2009; accepted 29 January 2009 相似文献
749.
S. K. Grant 《Cellular and molecular life sciences : CMLS》2009,66(7):1163-1177
Protein kinase inhibitors represent an important and still emerging class of targeted therapeutic agents. Drug discovery and
development strategies have explored numerous approaches to target the inhibition of protein kinase signaling. This review
will highlight some of the strategies that have led to the successful clinical development of therapeutic protein kinase inhibitors,
particularly as anticancer drugs. Some notable advances have been made in the development of novel protein and oligonucleotide-based
biologics that target growth factor or receptor tyrosine kinases. Also, advances have been made in the rational design of
small-molecule inhibitors that target unique kinase conformational forms and binding sites, and have specific kinase selectivity
profiles. A review will also be given of some of the potential clinical toxicities and adverse side-effects associated with
these kinase-targeted drugs. Therapeutic protein kinase inhibitors have been highly beneficial to cancer patients and offer
the promise of future therapies for other diseases as well.
Received 02 September 2008; received after revision 13 October 2008; accepted 15 October 2008 相似文献
750.
Decoding the Hedgehog signal in animal development 总被引:4,自引:0,他引:4
The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad of developmental processes via a complex signaling
cascade conserved in species ranging from insects to mammals. In many developmental contexts, Hh acts as long-range morphogen
to control distinct cellular outcomes as a function of its concentration. Here we review the current understanding of the
Hh signaling mechanisms that govern the establishment of the Hh gradient and the transduction of the Hh signal with an emphasis
on the intracellular signaling cascade from the receptor to the nuclear effector. We discuss how graded Hh signals are transduced
to govern distinct developmental outcomes.
Received 28 October 2005; received after revision 6 February 2006; accepted 15 February 2006 相似文献