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981.
Molecular mechanisms of spider silk 总被引:2,自引:0,他引:2
Hu X Vasanthavada K Kohler K McNary S Moore AM Vierra CA 《Cellular and molecular life sciences : CMLS》2006,63(17):1986-1999
Spiders spin high-performance silks through the expression and assembly of tissue-restricted fibroin proteins. Spider silks
are composite protein biopolymers that have complex microstructures. Retrieval of cDNAs and genomic DNAs encoding silk fibroins
has revealed an association between the protein sequences and structure-property relationships. However, before spider silks
can be subject to genetic engineering for commercial applications, the complete protein sequences and their functions, as
well as the details of the spinning mechanism, will require additional progress and collaborative efforts in the areas of
biochemistry, molecular biology and material science. Novel approaches to reveal additional molecular constituents embedded
in the spider fibers, as well as cloning strategies to manipulate the genes for expression, will continue to be important
aspects of spider biology research. Here we summarize the molecular characteristics of the different spider fibroins, the
mechanical properties and assembly process of spidroins and the advances in protein expression systems used for recombinant
silk production. We also highlight different technical approaches being used to elucidate the molecular constituents of silk
fibers.
Received 28 February 2006; received after revision 14 April 2006; accepted 22 May 2006
X. Hu and K. Vasanthavada contributed equally to this work. 相似文献
982.
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
983.
Shafqat J Melles E Sigmundsson K Johansson BL Ekberg K Alvelius G Henriksson M Johansson J Wahren J Jörnvall H 《Cellular and molecular life sciences : CMLS》2006,63(15):1805-1811
Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence
insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding,
while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide
lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin
oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin
and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting
insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically
at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the
beneficial effect of C-peptide and insulin replacement in type 1 diabetics.
Received 3 May 2006; received after revision 9 June 2006; accepted 12 June 2006 Free Online Access 相似文献
984.
Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type 总被引:10,自引:0,他引:10
Lerner-Ellis JP Tirone JC Pawelek PD Doré C Atkinson JL Watkins D Morel CF Fujiwara TM Moras E Hosack AR Dunbar GV Antonicka H Forgetta V Dobson CM Leclerc D Gravel RA Shoubridge EA Coulton JW Lepage P Rommens JM Morgan K Rosenblatt DS 《Nature genetics》2006,38(1):93-100
Methylmalonic aciduria and homocystinuria, cblC type (OMIM 277400), is the most common inborn error of vitamin B(12) (cobalamin) metabolism, with about 250 known cases. Affected individuals have developmental, hematological, neurological, metabolic, ophthalmologic and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. The cblC locus was mapped to chromosome region 1p by linkage analysis. We refined the chromosomal interval using homozygosity mapping and haplotype analyses and identified the MMACHC gene. In 204 individuals, 42 different mutations were identified, many consistent with a loss of function of the protein product. One mutation, 271dupA, accounted for 40% of all disease alleles. Transduction of wild-type MMACHC into immortalized cblC fibroblast cell lines corrected the cellular phenotype. Molecular modeling predicts that the C-terminal region of the gene product folds similarly to TonB, a bacterial protein involved in energy transduction for cobalamin uptake. 相似文献
985.
Uhland K 《Cellular and molecular life sciences : CMLS》2006,63(24):2968-2978
Tumor progression and metastasis are the pathologic effects of uncontrolled or deregulated invasive growth, a process in which
proteases play a fundamental role. They mediate the degradation of extracellular matrix components and intercellular cohesive
structures to allow migration of the cells into the extracellular environment and activate growth and angiogenic factors.
In addition to metalloproteases and the plasminogen activation system, another protease, matriptase, contributes substantially
to these processes. Matriptase is a type II transmembrane trypsin-like serine protease that is expressed by cells of epithelial
origin and is overexpressed in a variety of human cancers. It has been suggested that this protease not only facilitates cellular
invasiveness but may also activate oncogenic pathways. This review summarizes current knowledge about matriptase, its putative
role in tumor initiation and progression, and its potential as a novel target in anti-cancer therapy.
Received 29 June 2006; received after revision 1 August 2006; accepted 19 September 2006 相似文献
986.
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
987.
The xylosyltransferases I and II (XT-I, XT-II, EC 2.4.2.26) catalyze the transfer of xylose from UDP-xylose to selected serine
residues in the proteoglycan core protein, which is the initial and ratelimiting step in glycosaminoglycan biosynthesis. Both
xylosyltransferases are Golgi-resident enzymes and transfer xylose to similar core proteins acceptors. XT-I and XT-II are
differentially expressed in cell types and tissues, although the reason for the existence of two xylosyltransferase isoforms
in all higher organisms remains elusive. Serum xylosyltransferase activity was found to be a biochemical marker for the assessment
of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes. Furthermore, sequence variations
in the XT-I and XT-II coding genes were identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma
elasticum. These findings point to the important role of the xylosyltransferases as disease modifiers in pathologies which
are characterized by an altered proteoglycan metabolism. The present review discusses recent advances in mammalian xylosyltransferases
and the impact of xylosyltransferases in proteoglycan-associated diseases.
Received 9 February 2007; accepted 5 March 2007 相似文献
988.
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
989.
990.
Mailman MD Feolo M Jin Y Kimura M Tryka K Bagoutdinov R Hao L Kiang A Paschall J Phan L Popova N Pretel S Ziyabari L Lee M Shao Y Wang ZY Sirotkin K Ward M Kholodov M Zbicz K Beck J Kimelman M Shevelev S Preuss D Yaschenko E Graeff A Ostell J Sherry ST 《Nature genetics》2007,39(10):1181-1186
The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data. 相似文献