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171.
172.
Blasic JR Lane Brown R Robinson PR 《Cellular and molecular life sciences : CMLS》2012,69(9):1551-1562
Melanopsin-based phototransduction is involved in non-image forming light responses including circadian entrainment, pupil
constriction, suppression of pineal melatonin synthesis, and direct photic regulation of sleep in vertebrates. Given that
the functions of melanopsin involve the measurement and summation of total environmental luminance, there would appear to
be no need for the rapid deactivation typical of other G-protein coupled receptors. In this study, however, we demonstrate
that heterologously expressed mouse melanopsin is phosphorylated in a light-dependent manner, and that this phosphorylation
is involved in regulating the rate of G-protein activation and the lifetime of melanopsin’s active state. Furthermore, we
provide evidence for light-dependent phosphorylation of melanopsin in the mouse retina using an in situ proximity ligation
assay. Finally, we demonstrate that melanopsin preferentially interacts with the GRK2/3 family of G-protein coupled receptor
kinases through co-immunoprecipitation assays. Based on the complement of G-protein receptor kinases present in the melanopsin-expressing
retinal ganglion cells, GRK2 emerges as the best candidate for melanopsin’s cognate GRK. 相似文献
173.
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
174.
Double-strand breaks (DSBs) are the most detrimental form of DNA damage. Failure to repair these cytotoxic lesions can result
in genome rearrangements conducive to the development of many diseases, including cancer. The DNA damage response (DDR) ensures
the rapid detection and repair of DSBs in order to maintain genome integrity. Central to the DDR are the DNA damage checkpoints.
When activated by DNA damage, these sophisticated surveillance mechanisms induce transient cell cycle arrests, allowing sufficient
time for DNA repair. Since the term “checkpoint” was coined over 20 years ago, our understanding of the molecular mechanisms
governing the DNA damage checkpoint has advanced significantly. These pathways are highly conserved from yeast to humans.
Thus, significant findings in yeast may be extrapolated to vertebrates, greatly facilitating the molecular dissection of these
complex regulatory networks. This review focuses on the cellular response to DSBs in Saccharomyces cerevisiae, providing a comprehensive overview of how these signalling pathways function to orchestrate the cellular response to DNA
damage and preserve genome stability in eukaryotic cells. 相似文献
175.
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
176.
Valiokas R 《Cellular and molecular life sciences : CMLS》2012,69(3):347-356
The actual progress towards biological chip devices consisting of nanostructured functional entities is summarized. The practical
aspects of molecular nanobiochips are discussed, including the main surface chemistry platforms, as well as conventional and
unconventional fabrication tools. Several successful biological demonstrations of the first generation of nanobiochip devices
(mainly, different nanoarrays) are highlighted with the aim of revealing the potential of this technology in life sciences,
medicine, and related areas. 相似文献
177.
Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune
response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement
of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and
chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released
from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated
in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can
initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize
the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous
TLR ligands in the tumorigenesis. 相似文献
178.
179.
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
180.
Sieni E Cetica V Mastrodicasa E Pende D Moretta L Griffiths G Aricò M 《Cellular and molecular life sciences : CMLS》2012,69(1):29-40
Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited
human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical
syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these
patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce
a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic
approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated
cellular cytotoxicity in humans. 相似文献