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81.
82.
Mansi Gupta Anja Machate Daniela Zöller Michael Brand 《Genesis (New York, N.Y. : 2000)》2016,54(1):19-28
Gene trapping has emerged as a valuable tool to create conditional alleles in various model organisms. Here we report the FLEx‐based gene trap vector SAGFLEx that allows the generation of conditional mutations in zebrafish by gene‐trap mutagenesis. The SAGFLEx gene‐trap cassette comprises the rabbit β‐globin splice acceptor and the coding sequence of GFP, flanked by pairs of inversely oriented heterotypic target sites for the site‐specific recombinases Cre and Flp. Insertion of the gene‐trap cassette into endogenous genes can result in conditional mutations that are stably inverted by Cre and Flp, respectively. To test the functionality of this system we performed a pilot screen and analyzed the insertion of the gene‐trap cassette into the lima1a gene locus. In this lima1a allele, GFP expression faithfully recapitulated the endogenous lima1a expression and resulted in a complete knockout of the gene in homozygosity. Application of either Cre or Flp was able to mediate the stable inversion of the gene trap cassette and showed the ability to conditionally rescue or reintroduce the gene inactivation. Combined with pharmacologically inducible site specific recombinases the SAGFLEx vector insertions will enable precise conditional knockout studies in a spatial‐ and temporal‐controlled manner. genesis 54:19–28, 2016. © 2015 Wiley Periodicals, Inc. 相似文献
83.
Andrei Prodan Sultan Imangaliyev Henk S. Brand Martijn N. A. Rosema Evgeni Levin Wim Crielaard Bart J. F. Keijser Enno C. I. Veerman 《Metabolomics : Official journal of the Metabolomic Society》2016,12(9):147
Introduction
Understanding the changes occurring in the oral ecosystem during development of gingivitis could help improve prevention and treatment strategies for oral health. Erythritol is a non-caloric polyol proposed to have beneficial effects on oral health.Objectives
To examine the effect of experimental gingivitis and the effect of erythritol on the salivary metabolome and salivary functional biochemistry.Methods
In a two-week experimental gingivitis challenge intervention study, non-targeted, mass spectrometry-based metabolomic profiling was performed on saliva samples from 61 healthy adults, collected at five time-points. The effect of erythritol was studied in a randomized, controlled trial setting. Fourteen salivary biochemistry variables were measured with antibody- or enzymatic activity-based assays.Results
Bacterial amino acid catabolites (cadaverine, N-acetylcadaverine, and α-hydroxyisovalerate) and end-products of bacterial alkali-producing pathways (N-α-acetylornithine and γ-aminobutyrate) increased significantly during the experimental gingivitis. Significant changes were found in a set of 13 salivary metabolite ratios composed of host cell membrane lipids involved in cell signaling, host responses to bacteria, and defense against free radicals. An increase in mevalonate was also observed. There were no significant effects of erythritol. No significant changes were found in functional salivary biochemistry.Conclusions
The findings underline a dynamic interaction between the host and the oral microbial biofilm during an experimental induction of gingivitis.84.
Interactions and subcellular distribution of DNA replication initiation proteins in eukaryotic cells
For initiation of eukaryotic DNA replication the origin recognition complex (ORC) associates with chromatin sites and constitutes
a landing pad allowing Cdc6, Cdt1 and MCM proteins to accomplish the pre-replication complex (pre-RC). In S phase, the putative
MCM helicase is assumed to move away from the ORC to trigger DNA unwinding. By using the fluorescence-based assays bioluminescence
resonance energy transfer (BRET) and bimolecular fluorescence complementation (BiFC) we show in live mammalian cells that
one key interaction in pre-RC assembly, the interaction between Orc2 and Orc3, is not restricted to the nucleus but also occurs
in the cytoplasm. BRET assays also revealed a direct interaction between Orc2 and nuclear localization signal (NLS)-depleted
Orc3. Further, we assessed the subcellular distribution of Orc2 and Orc3 in relation to MCM proteins Mcm3 and Mcm6 as well
as to a key protein involved in elongation of DNA replication, proliferating nuclear cell antigen (PCNA). Our findings illustrate
the spatial complexity of the elaborated process of DNA replication as well as that the BRET and BiFC techniques are novel
tools that could contribute to our understanding of the processes at the very beginning of the duplication of the genome. 相似文献
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Barton PJ Cullen ME Townsend PJ Brand NJ Mullen AJ Norman DA Bhavsar PK Yacoub MH 《Genomics》1999,57(1):102-109
Based on chromosomal mapping data, we recently revealed an unexpected linkage of troponin genes in the human genome: the six genes encoding striated muscle troponin I and troponin T isoforms are located at three chromosomal sites, each of which carries a troponin I-troponin T gene pair. Here we have investigated the organization of these genes at the DNA level in isolated P1 and PAC genomic clones and demonstrate close physical linkage in two cases through the isolation of individual clones containing a complete troponin I-troponin T gene pair. As an initial step toward fully characterizing this pattern of linkage, we have determined the organization and complete sequence of the locus encoding cardiac troponin I and slow skeletal troponin T and thereby also provide the first determination of the structure and sequence of a slow skeletal troponin T gene. Our data show that the genes are organized head to tail and are separated by only 2.6 kb of intervening sequence. In contrast to other troponin genes, and despite their close proximity, the cardiac troponin I and slow skeletal troponin T genes show independent tissue-specific expression. Such close physical linkage has implications for the evolution of the troponin gene families, for their regulation, and for the analysis of mutations implicated in cardiomyopathy. 相似文献
89.
Page S Fischer C Baumgartner B Haas M Kreusel U Loidl G Hayn M Ziegler-Heitbrock HW Neumeier D Brand K 《The Journal of biological chemistry》1999,274(17):11611-11618
90.
Loeffler SH de Vries MJ Schukken YH de Zeeuw AC Dijkhuizen AA de Graaf FM Brand A 《Theriogenology》1999,51(7):1267-1284
Technicians recorded body condition score (BCS) and several parameters related to estrus and/or metritis for 1694 first insemination cows on 23 farms. Additional variables for modeling the adjusted odds ratios (OR) for pregnancy were data on disease prior to or within 21 days of AI and test day milk yields. Significant predictors for pregnancy were farm, year and season, BCS, uterine tone, contaminated insemination gun after AI, fat-protein corrected kilograms milk (FPCM), days in milk (DIM), and diseases. Vaginal mucus, ease of cervical passage, and lameness were not significant predictors for pregnancy. Pregnancy risk at AI increased with increasing DIM, reaching a near optimum after 82 days. Lack of uterine tone was associated with a lowered pregnancy risk (OR = 0.69) as was contaminated insemination gun (OR = 0.67), first-parity lactation, FPCM >33 kg (OR = 0.71), BCS 2.5 at AI (OR = 0.65), clinical mastitis (OR = 0.53), cystic ovarian disease (OR = 0.53), and metritis (OR = 0.74). It was concluded that data on BCS and uterine findings, as collected by AI technicians, are significant predictors of AI outcome. Dairy producers and veterinarians should jointly examine the potential costs and value of such AI technician-based data to improve herd fertility. 相似文献