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排序方式: 共有496条查询结果,搜索用时 15 毫秒
491.
492.
Estrada K Styrkarsdottir U Evangelou E Hsu YH Duncan EL Ntzani EE Oei L Albagha OM Amin N Kemp JP Koller DL Li G Liu CT Minster RL Moayyeri A Vandenput L Willner D Xiao SM Yerges-Armstrong LM Zheng HF Alonso N Eriksson J Kammerer CM Kaptoge SK Leo PJ Thorleifsson G Wilson SG Wilson JF Aalto V Alen M Aragaki AK Aspelund T Center JR Dailiana Z Duggan DJ Garcia M Garcia-Giralt N Giroux S Hallmans G Hocking LJ Husted LB Jameson KA Khusainova R Kim GS Kooperberg C Koromila T Kruk M Laaksonen M 《Nature genetics》2012,44(5):491-501
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility. 相似文献
493.
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
494.
In the sixties James Watson suggested a twosite model for the ribosome comprising the P site for the peptidyl transfer RNA
(tRNA) before peptide-bond formation and the A site, where decoding takes place according to the codon exposed there. In the
eighties a third tRNA binding site was detected, the E site, which was specific for deacylated tRNA and turned out to be a
universal feature of ribosomes. However, despite having three tRNA binding sites, only two tRNAs occupy the ribosome at a
time during protein synthesis: at the A and P sites before translocation (PRE state) and at the P and E sites after translocation
(POST state). The importance of having two tRNAs in the POST state has been revealed during the last 25 years, showing that
the E site contributes two fundamental features: (i) the fact that incorporation of a wrong amino acid is not harmful for
the cell (only 1 in about 400 misincorporations destroys the function of a protein) stems from the presence of an E-tRNA;
(ii) maintenance of the reading frame is one of the most remarkable achievements of the ribosome, essential for faithful translation
of the genetic information. The presence of the POST state E-tRNA prevents loss of the reading frame.
Received 14 March 2006; received after revision 8 June 2006; accepted 4 August 2006 相似文献
495.
Even though cohabitation has become more prevalent in the last few decades, the majority of the adult population is married, and marriage is associated with a number of factors, such as educational outcom and health. Understanding the marrie population is also an important part of understanding partnering behaviour and family formation and dissolution. The length of marriages and whether they are ended by death or divorce is therefore of interest t demographers and policy maker 相似文献
496.
Barton A Thomson W Ke X Eyre S Hinks A Bowes J Plant D Gibbons LJ;Wellcome Trust Case Control Consortium;YEAR Consortium;BIRAC Consortium Wilson AG Bax DE Morgan AW Emery P Steer S Hocking L Reid DM Wordsworth P Harrison P Worthington J 《Nature genetics》2008,40(10):1156-1159
The WTCCC study identified 49 SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-4) - 1 x 10(-5) (tier 3). Here we show that three of these SNPs, mapping to chromosome 10p15 (rs4750316), 12q13 (rs1678542) and 22q13 (rs3218253), are also associated (trend P = 4 x 10(-5), P = 4 x 10(-4) and P = 4 x 10(-4), respectively) in a validation study of 4,106 individuals with rheumatoid arthritis and an expanded reference group of 11,238 subjects, confirming them as true susceptibility loci in individuals of European ancestry. 相似文献