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731.
The bugs that came in from the cold: molecular adaptations to low temperatures in insects 总被引:2,自引:0,他引:2
The widespread distribution of insects over many ecological niches is a testimony to their evolutionary success. The colonization
of environments at high latitudes or altitudes required the evolution of biochemical strategies that reduced the impact of
cold or freezing stress. This review focuses on our current interests in some of the genes and proteins involved in low temperature
survival in insects. Although the most widespread form of protection is the synthesis of low molecular weight polyol cryoprotectants,
proteins with intrinsic protective properties, such as the thermal hysteresis or antifreeze proteins are also important. These
have been cloned and characterized in certain moths and beetles. Molecular techniques allowing the isolation of genes differentially
regulated by low temperatures have revealed that heat shock proteins, cold stress proteins, membrane protectants, as well
as ice nucleators and other less well characterized proteins likely also play a role in cold hardiness.
Received 10 June 2008; received after revision 17 November 2008; accepted 18 November 2008 相似文献
732.
Epidemiological studies establish a link between Type 2 diabetes (T2DM) and Alzheimer’s disease (AD), both leading causes
of morbidity and mortality in the elderly. These diseases also share clinical and biochemical features suggesting common pathogenic
mechanisms. Specifically, both are amyloidoses as they are characterized by fibrillar protein aggregates – amylin in T2DM
pancreatic islets, and β-amyloid (Aβ) and neurofibrillary tangles (NFTs) in AD brain. Amylin aggregation is associated with
pancreatic β-cell loss, and Aβ and NFT formation with neuronal cell loss. We discuss the possibility that amylin and Aβ exert
their toxicity by similar mechanisms, with components of the pathocascades shared, and that therapies based on amyloidogenic
properties are beneficial for both T2DM and AD.
Received 27 January 2009; received after revision 17 February 2009; accepted 23 February 2009 相似文献
733.
Methionine adenosyltransferases (MATs) are the family of enzymes that synthesize the main biological methyl donor, S-adenosylmethionine. The high sequence conservation among catalytic subunits from bacteria and eukarya preserves key residues
that control activity and oligomerization, which is reflected in the protein structure. However, structural differences among
complexes with substrates and products have led to proposals of several reaction mechanisms. In parallel, folding studies
begin to explain how the three intertwined domains of the catalytic subunit are produced, and to highlight the importance
of certain intermediates in attaining the active final conformation. This review analyzes the available structural data and
proposes a consensus interpretation that facilitates an understanding of the pathological problems derived from impairment
of MAT function. In addition, new research opportunities directed toward clarification of aspects that remain obscure are
also identified.
Received 22 August 2008; received after revision 22 September 2008; accepted 26 September 2008 相似文献
734.
Epigenetic mechanisms in mammals 总被引:11,自引:1,他引:10
DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated
and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation
marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases,
there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several
lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated
in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian
epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during
mammalian development. 相似文献
735.
Pili in Gram-negative and Gram-positive bacteria — structure, assembly and their role in disease 总被引:2,自引:0,他引:2
Many bacterial species possess long filamentous structures known as pili or fimbriae extending from their surfaces. Despite
the diversity in pilus structure and biogenesis, pili in Gram-negative bacteria are typically formed by non-covalent homopolymerization
of major pilus subunit proteins (pilins), which generates the pilus shaft. Additional pilins may be added to the fiber and
often function as host cell adhesins. Some pili are also involved in biofilm formation, phage transduction, DNA uptake and
a special form of bacterial cell movement, known as ‘twitching motility’ In contrast, the more recently discovered pili in
Gram-positive bacteria are formed by covalent polymerization of pilin subunits in a process that requires a dedicated sortase
enzyme. Minor pilins are added to the fiber and play a major role in host cell colonization.
This review gives an overview of the structure, assembly and function of the best-characterized pili of both Gram-negative
and Gram-positive bacteria.
Received 08 August 2008; received after revision 24 September 2008; accepted 01 October 2008 相似文献
736.
Chronic granulomatous disease is an inherited disorder of the NADPH oxidase characterized by severe bacterial and fungal infections
and disordered inflammation. We propose that NADPH oxidase has a key role in regulating acute neutrophilic and T cell responses,
which in turn restrains fungal growth and calibrates the inflammatory response to minimize injury and allergy. In this model,
superoxide-induced activation of indoleamine 2,3-dioxygenase (IDO) is a central mechanism by which the optimal balance of
antifungal host defense and immune tolerance occurs. This model is based on studies in mice and requires correlation in humans.
Received 18 August 2008; received after revision 29 November 2008; accepted 16 December 2008 相似文献
737.
The synthesis of acute-phase protein serum amyloid A (SAA) is largely regulated by inflammation- associated cytokines and
a high concentration of circulating SAA may represent an ideal marker for acute and chronic inflammatory diseases. However,
SAA is also synthesized in extrahepatic tissues, e.g. human carcinoma metastases and cancer cell lines. An increasing body
of in vitro data supports the concept of involvement of SAA in carcinogenesis and neoplastic diseases. Accumulating evidence suggests
that SAA might be included in a group of biomarkers to detect a pattern of physiological events that reflect the growth of
malignancy and host response. This review is meant to provide a broad overview of the many ways that SAA could contribute
to tumour development, and accelerate tumour progression and metastasis, and to gain a better understanding of this acute-phase
reactant as a possible link between chronic inflammation and neoplasia.
Received 11 June 2008; received after revision 10 July 2008; accepted 28 July 2008 相似文献
738.
Inhibiting the production of amyloid-β by antagonising γ-secretase activity is currently being pursued as a therapeutic strategy
for Alzheimer’s disease (AD). However, early pre-clinical studies have demonstrated that disruption of presenilin-dependent
γ-secretase alters many presenilin-dependent processes, leading to early lethality in several AD model organisms. Subsequently,
transgenic animal studies have highlighted several gross developmental side effects arising from presenilin deficiency. Partial
knockdown or tissue-specific knockout of presenilins has identified the skin, vascular and immune systems as very sensitive
to loss of presenilin functions. A more appreciative understanding of presenilin biology is therefore demanded if γ-secretase
is to be pursued as a therapeutic target. Herein we review the current understanding of γ-secretase complexes; their regulation,
abundance of interacting partners and diversity of substrates. We also discuss regulation of the γ-secretase complexes, with
an emphasis on the functional role of presenilins in cell biology.
Received 25 July 2008; received after revision 24 November 2008; accepted 10 December 2008 相似文献
739.
740.
The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer.
Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation
into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair
processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch
repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated.
Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with
by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing
efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of
DNA repair in order to improve the efficacy of current anticancer treatments.
Received 08 September 2008; received after revision 25 September 2008; accepted 03 October 2008 相似文献