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Lucia Vernerova Frantisek Spoutil Miroslav Vlcek Katarina Krskova Adela Penesova Milada Meskova Andrea Marko Katarina Raslova Branislav Vohnout Jozef Rovensky Zdenko Killinger Ivana Jochmanova Ivica Lazurova Guenter Steiner Josef Smolen Richard Imrich 《PloS one》2016,11(4)
IntroductionThe aim of the study was to analyse genetic architecture of RA by utilizing multiparametric statistical methods such as linear discriminant analysis (LDA) and redundancy analysis (RDA).MethodsA total of 1393 volunteers, 499 patients with RA and 894 healthy controls were included in the study. The presence of shared epitope (SE) in HLA-DRB1 and 11 SNPs (PTPN22 C/T (rs2476601), STAT4 G/T (rs7574865), CTLA4 A/G (rs3087243), TRAF1/C5 A/G (rs3761847), IRF5 T/C (rs10488631), TNFAIP3 C/T (rs5029937), AFF3 A/T (rs11676922), PADI4 C/T (rs2240340), CD28 T/C (rs1980422), CSK G/A (rs34933034) and FCGR3A A/C (rs396991), rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) and clinical status was analysed using the LDA and RDA.ResultsHLA-DRB1, PTPN22, STAT4, IRF5 and PADI4 significantly discriminated between RA patients and healthy controls in LDA. The correlation between RA diagnosis and the explanatory variables in the model was 0.328 (Trace = 0.107; F = 13.715; P = 0.0002). The risk variants of IRF5 and CD28 genes were found to be common determinants for seropositivity in RDA, while positivity of RF alone was associated with the CTLA4 risk variant in heterozygous form. The correlation between serologic status and genetic determinants on the 1st ordinal axis was 0.468, and 0.145 on the 2nd one (Trace = 0.179; F = 6.135; P = 0.001). The risk alleles in AFF3 gene together with the presence of ACPA were associated with higher clinical severity of RA.ConclusionsThe association among multiple risk variants related to T cell receptor signalling with seropositivity may play an important role in distinct clinical phenotypes of RA. Our study demonstrates that multiparametric analyses represent a powerful tool for investigation of mutual relationships of potential risk factors in complex diseases such as RA. 相似文献
93.
Solution structure of the lymphocyte receptor Nkrp1a reveals a distinct conformation of the long loop region as compared to in the crystal structure 下载免费PDF全文
Daniel Rozbeský David Adámek Eliška Pospíšilová Petr Novák Josef Chmelík 《Proteins》2016,84(9):1304-1311
Mouse Nkrp1a receptor is a C‐type lectin‐like receptor expressed on the surface of natural killer cells that play an important role against virally infected and tumor cells. The recently solved crystal structure of Nkrp1a raises questions about a long loop region which was uniquely extended from the central region in the crystal. To understand the functional significance of the loop, the solution structure of Nkrp1a using nuclear magnetic resonance (NMR) spectroscopy was determined. A notable difference between the crystal and NMR structure of Nkrp1a appears in the conformation of the long loop region. While the extended loop points away from the central core and mediates formation of a domain swapped dimer in the crystal, the solution structure is monomeric with the loop tightly anchored to the central region. The findings described the first solution structure in the Nkrp1 family and revealed intriguing similarities and differences to the crystal structure. Proteins 2016; 84:1304–1311. © 2016 Wiley Periodicals, Inc. 相似文献
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Michael Meyer David Ott Philipp Gtze Heinz‐Josef Koch Christoph Scherber 《Ecology and evolution》2019,9(12):7307-7323
Agricultural landscapes are globally dominated by monocultures under intensive management. This is one of the main reasons for biodiversity loss and insect population decline in many regions all over the world. Agroecosystem biodiversity in these areas can be enhanced by cropping system diversification, such as crop rotations. Yet, long‐term studies on effects of crop rotations on aboveground agrobiodiversity are lacking. We set up a 10‐year long‐term crop rotation experiment in Central Germany and monitored the temporal dynamics of aboveground arthropods over a full cultivation period to investigate influence of current and preceding crop identity and cropping system diversification on activity density, species richness, and community structure. We found that species composition was strongly influenced by currently grown crop although effect on arthropods varied between species groups. Especially, winter oilseed rape strongly affects arthropod community structure. Interestingly, we were also able to show an influence of the preceding crops, indicating an ecological memory effect in the aboveground arthropod community. Our results show that crop identity of both currently and previously grown crops in crop rotations may lead to an increase in arthropod activity density and changes in species composition. Diversified crop rotations including appropriate crops can be an easily implemented tool to increase arthropod biodiversity and biomass at large spatial and temporal scales, particularly in areas dominated by a single crop (e.g., wheat, maize). Our results may help to design optimized crop rotations for large‐scale enhancement of insect biodiversity in agroecosystems. 相似文献
97.
Peptide O-xylosyltransferase (EC 2.4.2.26) is the first enzyme required for the generation of chondroitin and heparan sulfate glycosaminoglycan chains of proteoglycans. Cloning of cDNAs has previously shown that, whereas invertebrates generally have a single xylosyltransferase gene, vertebrate genomes encode two similar proteins, xylosyltransferase I and II (XT-I and XT-II). To date, enzymatic activity has only been demonstrated for the human XT-I, Caenorhabditis SQV-6, and Drosophila OXT isoforms. In the present study, we demonstrate that a soluble form of human XT-II expressed in the xylosyltransferase-deficient pgsA-745 (S745) Chinese hamster ovary cell line is indeed capable of catalyzing the transfer of xylose to a variety of peptide substrates; its enzyme activity was also proven using a Pichia-expressed form of XT-II. Its pH, temperature, and cation dependences are similar to those of XT-I expressed in either mammalian cells or yeast. Our data suggest that XT-I and XT-II are, at least in vitro, functionally identical. 相似文献
98.
Tykva R Hlavácek J Vlasáková V Cerný B Borovicková L Bennettová B Holík J Slaninová J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,848(2):258-263
Reversed-phase high-performance liquid radio-chromatography (radio-HPLC) was set up to detect the time course of labeled degradation product formation of the pentapeptide H-Tyr-Asp-Pro-Ala-Pro-OH (5P), which has oostatic effects in different insect species. The detection limit of the system was in the range of 80-150 Bq. To follow formation of the degradation products, three amino acid residues in 5P were independently tritiated: Tyr1, Pro3 and Pro5. Each of the three tritiated peptides was analyzed after incubation with fresh hemolymph or ovaries of Neobellieria bullata. In the incubation mixture, free terminal amino acids and shortened sequences of 5P were identified. A metabolite of tyrosine represented the only exception; it was finally identified as water using degradation of [3H]Tyr by tyrosinase. Metabolic degradation of [3H]Tyr-5P was found to be considerably quicker than that of H-[3H]Tyr-Asp-Pro-Ala-OH (4P). The degradation of 5P was considerably slower in ovaries in comparison to hemolymph. 相似文献
99.
Chmelik J 《Proteomics》2007,7(16):2719-2728
Field-flow fractionation (FFF) represents a group of elution separation methods where external force fields act perpendicularly on analytes in a carrier liquid flows with nonuniform velocity profiles. It is an elution separation method that enables to separate analytes in relatively short times and collect fractions for further characterization or for investigation of their properties. Other advantages of FFF are small consumption of samples and gentle experimental conditions. These make FFF uniquely qualified for separation and purification of biological samples. The most promising are applications of different variants of flow FFF utilizing a cross flow through membrane channel walls to separate proteins. The separation is based on differences in protein diffusion coefficients, which allows calculating the size of macromolecules. Other FFF techniques (e.g., electrical, isoelectric, and sedimentation FFF) were also used for separation of biomolecules. FFF appears to be not only promising rapid technique for protein separation but it offers some other advantages in sample preparation, especially, focusing (hyperlayer) FFF techniques that enable preparation of homogeneous fractions of cells. Selected applications of FFF to protein analysis are described and future trends in application of FFF to proteomics are discussed. 相似文献
100.
Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies 总被引:4,自引:0,他引:4
Hau P Jachimczak P Schlingensiepen R Schulmeyer F Jauch T Steinbrecher A Brawanski A Proescholdt M Schlaier J Buchroithner J Pichler J Wurm G Mehdorn M Strege R Schuierer G Villarrubia V Fellner F Jansen O Straube T Nohria V Goldbrunner M Kunst M Schmaus S Stauder G Bogdahn U Schlingensiepen KH 《Oligonucleotides》2007,17(2):201-212
Transforming growth factor-beta2 (TGF-beta2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-beta2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitro experiments have been performed to prove specificity and efficacy of the TGF-beta2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase I/II-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-beta2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-beta-2-overexpressing tumors. 相似文献