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871.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献
872.
Machnicka B Grochowalska R Bogusławska DM Sikorski AF Lecomte MC 《Cellular and molecular life sciences : CMLS》2012,69(2):191-201
This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning
the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering
protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight
recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many
cell types. 相似文献
873.
Xue B Mizianty MJ Kurgan L Uversky VN 《Cellular and molecular life sciences : CMLS》2012,69(8):1211-1259
Many proteins and protein regions are disordered in their native, biologically active states. These proteins/regions are abundant
in different organisms and carry out important biological functions that complement the functional repertoire of ordered proteins.
Viruses, with their highly compact genomes, small proteomes, and high adaptability for fast change in their biological and
physical environment utilize many of the advantages of intrinsic disorder. In fact, viral proteins are generally rich in intrinsic
disorder, and intrinsically disordered regions are commonly used by viruses to invade the host organisms, to hijack various
host systems, and to help viruses in accommodation to their hostile habitats and to manage their economic usage of genetic
material. In this review, we focus on the structural peculiarities of HIV-1 proteins, on the abundance of intrinsic disorder
in viral proteins, and on the role of intrinsic disorder in their functions. 相似文献
874.
Age is an important risk for autoimmunity, and many autoimmune diseases preferentially occur in the second half of adulthood
when immune competence has declined and thymic T cell generation has ceased. Many tolerance checkpoints have to fail for an
autoimmune disease to develop, and several of those are susceptible to the immune aging process. Homeostatic T cell proliferation
which is mainly responsible for T cell replenishment during adulthood can lead to the selection of T cells with increased
affinity to self- or neoantigens and enhanced growth and survival properties. These cells can acquire a memory-like phenotype,
in particular under lymphopenic conditions. Accumulation of end-differentiated effector T cells, either specific for self-antigen
or for latent viruses, have a low activation threshold due to the expression of signaling and regulatory molecules and generate
an inflammatory environment with their ability to be cytotoxic and to produce excessive amounts of cytokines and thereby inducing
or amplifying autoimmune responses. 相似文献
875.
Over the last two decades the molecular and cellular mechanisms underlying T cell activation, expansion, differentiation,
and memory formation have been intensively investigated. These studies revealed that the generation of memory T cells is critically
impacted by a number of factors, including the magnitude of the inflammatory response and cytokine production, the type of
dendritic cell [DC] that presents the pathogen derived antigen, their maturation status, and the concomitant provision of
costimulation. Nevertheless, the primary stimulus leading to T cell activation is generated through the T cell receptor [TCR]
following its engagement with a peptide MHC ligand [pMHC]. The purpose of this review is to highlight classical and recent
findings on how antigen recognition, the degree of TCR stimulation, and intracellular signal transduction pathways impact
the formation of effector and memory T cells. 相似文献
876.
877.
878.
Farooqui AA Farooqui T Panza F Frisardi V 《Cellular and molecular life sciences : CMLS》2012,69(5):741-762
The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin
resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation
in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone
released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the
hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic
syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism
underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However,
it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment
of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with
abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders
such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of
brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical
changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion
will initiate more studies on the relationship between metabolic syndrome and neurological disorders. 相似文献
879.
KI Cho K Searle M Webb H Yi PA Ferreira 《Cellular and molecular life sciences : CMLS》2012,69(20):3511-3527
Many components and pathways transducing multifaceted and deleterious effects of stress stimuli remain ill-defined. The Ran-binding protein 2 (RanBP2) interactome modulates the expression of a range of clinical and cell-context-dependent manifestations upon a variety of stressors. We examined the role of Ranbp2 haploinsufficiency on cellular and metabolic manifestations linked to tyrosine-hydroxylase (TH(+)) dopaminergic neurons and glial cells of the brain and retina upon acute challenge to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonian neurotoxin, which models facets of Parkinson disease. MPTP led to stronger akinetic parkinsonism and slower recovery in Ranbp2 (+/-) than wild-type mice without viability changes of brain TH(+)-neurons of either genotype, with the exception of transient nuclear atypia via changes in chromatin condensation of Ranbp2 (+/-) TH(+)-neurons. Conversely, the number of wild-type retinal TH(+)-amacrine neurons compared to Ranbp2 (+/-) underwent milder declines without apoptosis followed by stronger recoveries without neurogenesis. These phenotypes were accompanied by a stronger rise of EdU(+)-proliferative cells and non-proliferative gliosis of GFAP(+)-Müller cells in wild-type than Ranbp2 (+/-) that outlasted the MPTP-insult. Finally, MPTP-treated wild-type and Ranbp2 (+/-) mice present distinct metabolic footprints in the brain or selective regions thereof, such as striatum, that are supportive of RanBP2-mediated regulation of interdependent metabolic pathways of lysine, cholesterol, free-fatty acids, or their β-oxidation. These studies demonstrate contrasting gene-environment phenodeviances and roles of Ranbp2 between dopaminergic and glial cells of the brain and retina upon oxidative stress-elicited signaling and factors triggering a continuum of metabolic and cellular manifestations and proxies linked to oxidative stress, and chorioretinal and neurological disorders such as Parkinson. 相似文献
880.
van der Meijden PE Feijge MA Swieringa F Gilio K Nergiz-Unal R Hamulyák K Heemskerk JW 《Cellular and molecular life sciences : CMLS》2012,69(20):3481-3492
The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation. 相似文献