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61.
gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+) conductance, and glutamate flux 总被引:1,自引:0,他引:1
Patton HK Zhou ZH Bubien JK Benveniste EN Benos DJ 《American journal of physiology. Cell physiology》2000,279(3):C700-C708
Many human immunodeficiency virus(HIV)-infected patients suffer from impaired neurological function anddementia. This facet of the disease has been termed acquiredimmunodeficiency syndrome (AIDS)-associated dementia complex (ADC).Several cell types, including astrocytes and neurons, are notproductively infected by virus but are involved in ADC pathophysiology.Previous studies of rat astrocytes showed that an HIV coat protein(gp120) accelerated astrocyte Na+/H+ exchangeand that the resultant intracellular alkalinization activated apH-sensitive K+ conductance. The present experiments wereconducted to determine whether gp120 affected human astrocytes in thesame fashion. It was found that primary human astrocytes express apH-sensitive K+ conductance that was activated onintracellular alkalinization. Also, gp120 treatment of whole cellclamped human astrocytes activated this conductance specifically.Furthermore, gp120 inhibited glutamate uptake by primary humanastrocytes. These altered physiological processes could contribute topathophysiological changes in HIV-infected brains. Because thegp120-induced cell physiological changes were partially inhibited bydimethylamiloride (an inhibitor of Na+/H+exchange), our findings suggest that modification of human astrocyte Na+/H+ exchange activity may provide a means ofaddressing some of the neurological complications of HIV infection. 相似文献
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Aromatic amino acid hydroxylase (AAAH) genes and insulin-like genes form part of an extensive paralogy region shared by human chromosomes 11 and 12, thought to have arisen by tetraploidy in early vertebrate evolution. Cloning of a complementary DNA (cDNA) for an amphioxus (Branchiostoma floridae) hydroxylase gene (AmphiPAH) allowed us to investigate the ancestry of the human chromosome 11/12 paralogy region. Molecular phylogenetic evidence reveals that AmphiPAH is orthologous to vertebrate phenylalanine (PAH) genes; the implication is that all three vertebrate AAAH genes arose early in metazoan evolution, predating vertebrates. In contrast, our phylogenetic analysis of amphioxus and vertebrate insulin-related gene sequences is consistent with duplication of these genes during early chordate ancestry. The conclusion is that two tightly linked gene families on human chromosomes 11 and 12 were not duplicated coincidentally. We rationalize this paradox by invoking gene loss in the AAAH gene family and conclude that paralogous genes shared by paralogous chromosomes need not have identical evolutionary histories. 相似文献
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Ali BR Jeffery S Patel N Tinworth LE Meguid N Patton MA Afzal AR 《Human genetics》2007,122(3-4):389-395
ROR2 is a member of the cell surface receptor tyrosine kinase (RTKs) family of proteins and is involved in the developmental
morphogenesis of the skeletal, cardiovascular and genital systems. Mutations in ROR2 have been shown to cause two distinct
human disorders, autosomal recessive Robinow syndrome and dominantly inherited Brachydactyly type B. The recessive form of
Robinow syndrome is a disorder caused by loss-of-function mutations whereas Brachydactyly type B is a dominant disease and
is presumably caused by gain-of-function mutations in the same gene. We have previously established that all the missense
mutations causing Robinow syndrome in ROR2 are retained in the endoplasmic reticulum and therefore concluded that their loss
of function is due to a defect in their intracellular trafficking. These mutations were in the distal portion of the frizzled-like
cysteine rich domain and kringle domain. Here we report the identification of two novel mutations in the frizzled-like cysteine-rich
domain of ROR2 causing Robinow syndrome. We establish the retention of the mutated proteins in the endoplasmic reticulum of
HeLa cells and therefore failure to reach the plasma membrane. The clustering of Robinow-causing mutations in the extracellular
frizzled-like cysteine-rich domain of ROR2 suggests a stringent requirement for the correct folding of this domain prior to
export of ROR2 from the endoplasmic reticulum to the plasma membrane.
GenBank accession number ROR2, M97639. 相似文献
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Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.70.
Sigrid NW Vorrink Helianthe SM Kort Thierry Troosters Jan-Willem J Lammers 《Respiratory research》2011,12(1):33