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921.
Olfactory receptors typically exhibit poor plasma membrane localization and functionality when heterologously expressed in
most cell types. It has therefore proven difficult to effectively study olfactory receptor pharmacology and signaling mechanisms
using traditional cell culture systems. Over the past few years, a variety of distinct proteins have been reported to interact
with olfactory receptors and facilitate olfactory receptor trafficking to the plasma membrane in heterologous cells. Advances
in this area have shed significant light on the fundamental factors governing the cell-specific control of olfactory receptor
trafficking. 相似文献
922.
A. F. Vanin L. M. Bevers A. Slama-Schwok E. E. van Faassen 《Cellular and molecular life sciences : CMLS》2008,65(24):4066-4069
Announcement
Announcement 相似文献923.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
924.
It is generally thought that microtubule-associated motors insure long-range movements of the secretory vesicles from the center of the cell to its periphery, while myosins insure short-range movements at the cell periphery. However, several of the myosins that have been reported during the last decade to be involved in the exocytic pathway are not processive, meaning that they do not have the ability to move cargos along actin polymers. We will review here the possible mechanisms by which these myosins could contribute to the traffic of secretory proteins from the Golgi complex to the plasma membrane. 相似文献
925.
Papaconstantinou ME Gandhi PS Chen Z Bah A Di Cera E 《Cellular and molecular life sciences : CMLS》2008,65(22):3688-3697
Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na(+)-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 A resolution. The structure reveals a Na(+) binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na(+) binding to meizothrombin desF1 document a slow phase of fluorescence change with a k(obs) decreasing hyperbolically with increasing [Na(+)], consistent with the existence of three conformations in equilibrium, E*, E and E:Na(+), as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation. 相似文献
926.
Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state 总被引:1,自引:0,他引:1
Bergman T Zhang K Palmberg C Jörnvall H Auld DS 《Cellular and molecular life sciences : CMLS》2008,65(24):4019-4027
Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined
by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine
structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc
is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased
zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance
of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide
data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic
state, implying a functional nature for this zinc site.
Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008 相似文献
927.
Molecular mechanisms of phagocytic uptake in mammalian cells 总被引:2,自引:1,他引:1
Groves E Dart AE Covarelli V Caron E 《Cellular and molecular life sciences : CMLS》2008,65(13):1957-1976
Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process. 相似文献
928.
Galat A 《Cellular and molecular life sciences : CMLS》2008,65(21):3481-3493
Extracellular domains of some cellular receptors expressed in the organisms at different levels of development belong to three-fingered
protein (TFP) fold. The Homo sapiens genome encodes at least 45 genes containing from one to three TFP domains (TFPDs), namely diverse paralogues of the Ly6 gene,
CD59 and the receptors of activins, bone morphogenetic proteins, Mullerian inhibiting substance and transforming growth factor-β.
C4.4a and urokinase/plasminogen activatory receptor contain two and three TFPD repeats, respectively. These diverse proteins
have a low overall sequence similarity with each other and their hydrophobicity levels vary to a considerable degree. It is
suggested that sequence differentiation within the TFPD led to distinct groups of proteins whose attributes were optimized
to fit both the physicochemical properties specific to their functional microenvironment and selective targeting of their
highly diversified extracellular cofactors.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 7 August 2008; accepted 29 August 2008 相似文献
929.
Loos RJ Lindgren CM Li S Wheeler E Zhao JH Prokopenko I Inouye M Freathy RM Attwood AP Beckmann JS Berndt SI;Prostate Lung Colorectal Ovarian 《Nature genetics》2008,40(6):768-775
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits. 相似文献
930.
Kondo Y Shen L Cheng AS Ahmed S Boumber Y Charo C Yamochi T Urano T Furukawa K Kwabi-Addo B Gold DL Sekido Y Huang TH Issa JP 《Nature genetics》2008,40(6):741-750
Epigenetic silencing in cancer cells is mediated by at least two distinct histone modifications, polycomb-based histone H3 lysine 27 trimethylation (H3K27triM) and H3K9 dimethylation. The relationship between DNA hypermethylation and these histone modifications is not completely understood. Using chromatin immunoprecipitation microarrays (ChIP-chip) in prostate cancer cells compared to normal prostate, we found that up to 5% of promoters (16% CpG islands and 84% non-CpG islands) were enriched with H3K27triM. These genes were silenced specifically in prostate cancer, and those CpG islands affected showed low levels of DNA methylation. Downregulation of the EZH2 histone methyltransferase restored expression of the H3K27triM target genes alone or in synergy with histone deacetylase inhibition, without affecting promoter DNA methylation, and with no effect on the expression of genes silenced by DNA hypermethylation. These data establish EZH2-mediated H3K27triM as a mechanism of tumor-suppressor gene silencing in cancer that is potentially independent of promoter DNA methylation. 相似文献