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891.
A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region 总被引:1,自引:0,他引:1
Smyth DJ Cooper JD Bailey R Field S Burren O Smink LJ Guja C Ionescu-Tirgoviste C Widmer B Dunger DB Savage DA Walker NM Clayton DG Todd JA 《Nature genetics》2006,38(6):617-619
In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10). 相似文献
892.
Rohmann E Brunner HG Kayserili H Uyguner O Nürnberg G Lew ED Dobbie A Eswarakumar VP Uzumcu A Ulubil-Emeroglu M Leroy JG Li Y Becker C Lehnerdt K Cremers CW Yüksel-Apak M Nürnberg P Kubisch C Kubisch C Schlessinger J van Bokhoven H Wollnik B 《Nature genetics》2006,38(4):414-417
Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by lacrimal duct aplasia, malformed ears and deafness, small teeth and digital anomalies. We identified heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3) in LADD families, and in one further LADD family, we detected a mutation in the gene encoding fibroblast growth factor 10 (FGF10), a known FGFR ligand. These findings increase the spectrum of anomalies associated with abnormal FGF signaling. 相似文献
893.
Capel B 《Nature genetics》2006,38(11):1233-1234
894.
Germline KRAS mutations cause Noonan syndrome 总被引:22,自引:0,他引:22
Schubbert S Zenker M Rowe SL Böll S Klein C Bollag G van der Burgt I Musante L Kalscheuer V Wehner LE Nguyen H West B Zhang KY Sistermans E Rauch A Niemeyer CM Shannon K Kratz CP 《Nature genetics》2006,38(3):331-336
Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream effectors, including Ras. We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome. Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner. These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras. 相似文献
895.
Despite the current availability of several hundreds of thousands of amino acid sequences, more than 39% of the well-defined
enzyme activities (EC numbers) are not associated with any sequence in major public databases. This wide gap separating knowledge
of biochemical function and sequence information is found in nearly all classes of enzymes. Thus, there is an urgent need
to explore the 1525 orphan enzymes (EC numbers without associated sequences), in order to progressively bridge this unwanted
gap. Improving genome annotation could unveil a significant proportion of sequenceless enzymes. Peptide mass mapping and further
genome mining would be useful to identify proper sequence for enzymes found in species for which genetic tools are missing.
Finally, the whole community must help major public databases to begin addressing the problem of missing or incomplete information.
Received 31 October 2005; received after revision 8 December 2005; accepted 20 December 2005 相似文献
896.
897.
Pocsai K Kosztka L Bakondi G Gönczi M Fodor J Dienes B Szentesi P Kovács I Feniger-Barish R Kopf E Zharhary D Szucs G Csernoch L Rusznák Z 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2364-2376
Amplification of the kcnk9 gene and overexpression of the encoded channel protein (TASK-3) seems to be involved in carcinogenesis. In the present work, TASK-3 expression of melanoma cells has been studied. For the investigation of TASK-3-specific immunolabelling, a monoclonal antibody has been developed and applied along with two, commercially available polyclonal antibodies targeting different epitopes of the channel protein. Both primary and metastatic melanoma cells proved to be TASK-3 positive, showing prominent intracellular TASK-3-specific labelling; mostly concentrating around or in the proximity of the nuclei. The immunoreaction was associated with the nuclear envelope, and with the processes of the cells and it was also present in the cell surface membrane. Specificity of the immunolabelling was confirmed by Western blot and transfection experiments. As TASK-3 immunopositivity of benign melanocytes could also be demonstrated, the presence or absence of TASK-3 channels cannot differentiate between malignant and non-malignant melanocytic tumours. 相似文献
898.
Gbaguidi B Hakizimana P Vandenbussche G Ruysschaert JM 《Cellular and molecular life sciences : CMLS》2007,64(12):1571-1582
LmrP is an electrogenic H+/drug antiporter that extrudes a broad spectrum of antibiotics. Five carboxylic residues are implicated in drug binding (Asp142
and Glu327) and proton motive force-mediated restructuring (Asp68, Asp128 and Asp235). ATR-FTIR (Attenuated Total Reflection
– Fourier Transform Infrared) and tryptophan quenching experiments revealed that phosphatidylethanolamine (PE) is required
to generate the structural intermediates induced by ionization of carboxylic residues. Surprisingly, no ionization-induced
conformational changes were detectable in the absence of PE, suggesting either that carboxylic acid residues do not ionize
or that ionization does not lead to any conformational change. The mean pKa of carboxylic residues evaluated by ATR-FTIR spectroscopy
was 6.5 for LmrP reconstituted in PE liposomes, whereas the pKa calculated in the absence of PE was 4.6. Considering that
16 of the 19 carboxylic residues are located in the extramembrane loops, the pKa values obtained in the absence and in the
presence of PE suggest that the interaction of the loop acid residues with the membrane interface depends on the lipid composition.
Received 23 January 2007; received after revision 2 April 2007; accepted 20 April 2007 相似文献
899.
Talavera K Ninomiya Y Winkel C Voets T Nilius B 《Cellular and molecular life sciences : CMLS》2007,64(4):377-381
Daily experience tells us that temperature has a strong influence on how we taste. Despite the longstanding interest of many
specialists in this aspect of taste, we are only starting to understand the molecular mechanisms underlying the temperature
dependence of different taste modalities. Recent research has led to the identification of some strong thermosensitive molecules
in the taste transduction pathway. The cold activation of the epithelial Na+ channel and the heat activation of the taste variant of the vanilloid receptor (TRPV1t) may underlie the temperature dependence
of salt responses. Heat activation of the transient receptor potential channel TRPM5 explains the enhancement of sweet taste
perception by warm temperatures. Current development of methods to study taste cell physiology will help to determine the
contribution of other temperature-sensitive events in the taste transduction pathways. Vice versa, the analysis of the thermodynamic properties of these events may assist to unveil the nature of several taste processes.
Received 29 August 2006; received after revision 5 October 2006; accepted 20 November 2006 相似文献
900.
Zhu X Su B Wang X Smith MA Perry G 《Cellular and molecular life sciences : CMLS》2007,64(17):2202-2210
Oxidative stress is one of the earliest events of Alzheimer disease (AD), with implications as an important mediator in the
onset, progression and pathogenesis of the disease. The generation of reactive oxygen species (ROS) and its consequent cellular
damage/response contributes to much of the hallmark AD pathology seen in susceptible neurons. The sources of ROS-mediated
damage appear to be multi-faceted in AD, with interactions between abnormal mitochondria, redox transition metals, and other
factors. In this review, we provide an overview of these potential causes of oxidative stress in AD. 相似文献