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91.
Anne Popescu Anna-Britta Hörnfeldt Salo Gronowitz 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1233-1249
Abstract Some carbocyclic uridines and cytidines have been prepared in a palladium-catalyzed reaction between 5-substituted uracils and cytosines and diacetoxymethylcyclopentene, prepared in a Prins reaction. The antiviral activity of the nucleoside analogues have been tested. 相似文献
92.
Effects of warming on root morphology, root mass distribution and microbial activity were studied in organic and mineral soil layers in two alpine ecosystems over>10 yr, using open-top chambers, in Swedish Lapland. Root mass was estimated using soil cores. Washed roots were scanned and sorted into four diameter classes, for which variables including root mass (g dry matter (g DM) m(-2)), root length density (RLD; cm cm(-3) soil), specific root length (SRL; m g DM(-1)), specific root area (SRA; m2 kg DM(-1)), and number of root tips m(-2) were determined. Nitrification (NEA) and denitrification enzyme activity (DEA) in the top 10 cm of soil were measured. Soil warming shifted the rooting zone towards the upper soil organic layer in both plant communities. In the dry heath, warming increased SRL and SRA of the finest roots in both soil layers, whereas the dry meadow was unaffected. Neither NEA nor DEA exhibited differences attributable to warming. Tundra plants may respond to climate change by altering their root morphology and mass while microbial activity may be unaffected. This suggests that carbon may be incorporated in tundra soils partly as a result of increases in the mass of the finer roots if temperatures rise. 相似文献
93.
Kaye SM Pietiläinen KH Kotronen A Joutsi-Korhonen L Kaprio J Yki-Järvinen H Silveira A Hamsten A Lassila R Rissanen A 《Obesity (Silver Spring, Md.)》2012,20(1):88-94
Coagulation and fibrinolytic activities are under strong genetic control. We studied the effects of acquired obesity, independent of genetic factors on coagulation and fibrinolysis activities in obesity-discordant healthy monozygotic (MZ) twin pairs. Fourteen obesity-discordant (BMI within-pair difference >3 kg/m(2)) and 10 concordant (BMI difference <2 kg/m(2)) MZ twin pairs were identified from the nationwide FinnTwin16 study. Body composition (dual-energy x-ray absorptiometry), abdominal fat distribution (magnetic resonance imaging), liver fat (magnetic resonance spectroscopy), high sensitivity C-reactive protein, insulin sensitivity (euglycemic hyperinsulinemic clamp), and a panel of different markers of blood coagulation and fibrinolysis in the fasting state were measured. Strong resemblance was observed in most coagulation factors within all twin pairs, with the intraclass correlations ranging from 0.73 to 0.97, P < 0.03. However, the activities of fibrinogen and FIX, FXI, and FXII, and plasminogen activator inhibitor-1 (PAI-1) activities were increased in the obese co-twins (P < 0.05) and strongly correlated with the measures of adiposity, inflammation, and insulin resistance (r = 0.32-0.73, P < 0.05) among the twin individuals. Intrapair differences in fibrinogen and PAI-1 correlated with those in BMI, adiposity, and fasting insulin levels (r = 0.40-0.58, P < 0.05) indicating the independent effect of obesity. Derangements of blood coagulation and fibrinolysis are present already in early adulthood in obese subjects. Acquired obesity, independent of genetic factors, increases the activities of fibrinogen and activities of FIX, FXI, FXII, and PAI-1. This study confirms the mechanisms of simultaneous activities of intrinsic coagulation factors and impaired fibrinolysis predisposing obese subjects to thrombosis. 相似文献
94.
Magnus Nilsson Anna Karin Belfrage Stefan Lindström Horst Wähling Charlotta Lindquist Susana Ayesa Pia Kahnberg Mikael Pelcman Kurt Benkestock Tatiana Agback Lotta Vrang Ylva Terelius Kristina Wikström Elizabeth Hamelink Christina Rydergård Michael Edlund Anders Eneroth Pierre Raboisson Tse-I Lin Herman de Kock Åsa Rosenquist 《Bioorganic & medicinal chemistry letters》2010,20(14):4004-4011
Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. 相似文献
95.
Anita Laitinen Sofia Oja Lotta Kilpinen Tanja Kaartinen Johanna Möller Saara Laitinen Matti Korhonen Johanna Nystedt 《Cytotechnology》2016,68(4):891-906
Efficient xenofree expansion methods to replace fetal bovine serum (FBS)-based culture methods are strongly encouraged by the regulators and are needed to facilitate the adoption of mesenchymal stromal cell (MSC)-based therapies. In the current study we established a clinically-compliant and reproducible animal serum-free culture protocol for bone marrow-(BM-) MSCs based on an optimized platelet-derived supplement. Our study compared two different platelet-derived supplements, platelet lysate PL1 versus PL2, produced by two different methods and lysed with different amounts of freeze–thaw cycles. Our study also explored the effect of a low oxygen concentration on BM-MSCs. FBS-supplemented BM-MSC culture served as control. Growth kinetics, differentiation and immunomodulatory potential, morphology, karyotype and immunophenotype was analysed. Growth kinetics in long-term culture was also studied. Based on the initial results, we chose to further process develop the PL1-supplemented culture protocol at 20 % oxygen. The results from 11 individual BM-MSC batches expanded in the chosen condition were consistent, yielding 6.60 × 109 ± 4.74 × 109 cells from only 20 ml of bone marrow. The cells suppressed T-cell proliferation, displayed normal karyotype and typical MSC differentiation potential and phenotype. The BM-MSCs were, however, consistently HLA-DR positive when cultured in platelet lysate (7.5–66.1 %). We additionally show that culture media antibiotics and sterile filtration of the platelet lysate can be successfully omitted. We present a robust and reproducible clinically-compliant culture method for BM-MSCs based on platelet lysate, which enables high quantities of HLA-DR positive MSCs at a low passage number (p2) and suitable for clinical use. 相似文献
96.
Background
The formation of native disulfide bonds is a complex and essential post-translational modification for many proteins. The large scale production of these proteins can be difficult and depends on targeting the protein to a compartment in which disulfide bond formation naturally occurs, usually the endoplasmic reticulum of eukaryotes or the periplasm of prokaryotes. It is currently thought to be impossible to produce large amounts of disulfide bond containing protein in the cytoplasm of wild-type bacteria such as E. coli due to the presence of multiple pathways for their reduction. 相似文献97.
Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen 《Immunogenetics》2009,61(4):247-256
Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune
and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the
DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional
genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging
single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to
validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were
genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy.
The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously
determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease
risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95%
to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk
effects. The method is transferable between populations and therefore suited for large-scale research studies and screening
of celiac disease among high-risk individuals or at the population level.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Lotta Koskinen and Jihane Romanos are authors with equal contribution. 相似文献
98.
Charlotte Ytterberg Sverker Johansson Kristina Gottberg Lotta Widén Holmqvist Lena von Koch 《BMC neurology》2008,8(1):36
Background
Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration. 相似文献99.
Poplawski AB Mårtensson L Wartiainen I Rasmussen U 《Journal of microbiological methods》2007,69(1):161-173
The aim of this study was to analyze a total euryarchaeal community at DNA and RNA levels in a Swedish barley field with relation to soil depth (0-10 and 20-30 cm layers), soil fraction (bulk soil and rhizosphere) and time (August and November sample collection). Amplification of 16S rRNA gene using the archaeal universal A2F and Euryarchaea specific EK510R/(EURY498) primer pair, combined with denaturing gradient gel electrophoresis (DGGE), revealed distinct differences between rDNA and rRNA DGGE profiles. The soil depth, time, or rhizosphere effects did not significantly influence Archaeal community structure. Surprisingly, sequence analysis of DGGE-derived amplicons revealed the presence of Euryarchaea as well as uncultured soil Crenarchaea affiliated with group 1. In agreement, sequence comparison analyses showed that the majority of uncultured Crenarchaea group 1 had almost 100% sequence complementarity to the 3' end of the EK510R/(EURY498) primer. Therefore, we propose that EK510R/(EURY498R) is a universal archaeal primer rather than a Euryarchaea specific SSUrRNA primer. Hence, considerable care should be taken during application of this primer in studies of euryarchaeal biodiversity in soil environments. 相似文献
100.
Jukka Jokinen Hanna Rinta-Kokko Lotta Siira Arto A. Palmu Mikko J. Virtanen Hanna Nohynek Anni Virolainen-Julkunen Maija Toropainen J. Pekka Nuorti 《PloS one》2015,10(3)