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71.
Demirkan A van Duijn CM Ugocsai P Isaacs A Pramstaller PP Liebisch G Wilson JF Johansson Å Rudan I Aulchenko YS Kirichenko AV Janssens AC Jansen RC Gnewuch C Domingues FS Pattaro C Wild SH Jonasson I Polasek O Zorkoltseva IV Hofman A Karssen LC Struchalin M Floyd J Igl W Biloglav Z Broer L Pfeufer A Pichler I Campbell S Zaboli G Kolcic I Rivadeneira F Huffman J Hastie ND Uitterlinden A Franke L Franklin CS Vitart V;DIAGRAM Consortium Nelson CP Preuss M;CARDIoGRAM Consortium Bis JC O'Donnell CJ 《PLoS genetics》2012,8(2):e1002490
Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10−204) and 10 loci for sphingolipids (smallest P-value = 3.10×10−57). After a correction for multiple comparisons (P-value<2.2×10−9), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits. 相似文献
72.
Anatoly S. Karavaev Anatoly S. Borovik Ekaterina I. Borovkova Eugeniya A. Orlova Margarita A. Simonyan Vladimir I. Ponomarenko Viktoriia V. Skazkina Vladimir I. Gridnev Boris P. Bezruchko Mikhail D. Prokhorov Anton R. Kiselev 《Biophysical journal》2021,120(13):2657-2664
The question of how much information the photoplethysmogram (PPG) signal contains on the autonomic regulation of blood pressure (BP) remains unsolved. This study aims to compare the low-frequency (LF) and high-frequency components of PPG and BP and assess their correlation with oscillations in interbeat (RR) intervals at similar frequencies. The PPG signal from the distal phalanx of the right index finger recorded using a reflective PPG sensor at green light, the BP signal from the left hand recorded using a Finometer, and RR intervals were analyzed. These signals were simultaneously recorded within 15 min in a supine resting condition in 17 healthy subjects (12 males and 5 females) aged 33 ± 9 years (mean ± SD). The study revealed the high coherence of LF components of PPG and BP with the LF component of RR intervals. The high-frequency components of these signals had low coherence. The analysis of the signal instantaneous phases revealed the presence of high-phase coherence between the LF components of PPG and BP. It is shown that the LF component of PPG is determined not only by local myogenic activity but also reflects the processes of autonomic control of BP. 相似文献
73.
Selective ‘stencil’-aided pre-PCR cleavage of wild-type sequences as a novel approach to detection of mutant K-RAS 下载免费PDF全文
Anatoly V. Lichtenstein Olga I. Serdjuk Tatjana I. Sukhova Hovsep S. Melkonyan Samuil R. Umansky 《Nucleic acids research》2001,29(17):e90
The enriched PCR widely used for detection of mutant K-RAS in either tumor tissues or circulating DNA was modified so that abundant wild-type K-RAS alleles are cleaved prior to PCR. We took advantage of an AluI recognition site located immediately upstream of the K-RAS codon 12. The site was reconstituted upon DNA denaturation followed by annealing with a ‘stencil’, a 16-bp synthetic oligonucleotide complementary to the wild-type sequence. As opposed to normal K-RAS, the mutant allele forms, upon annealing with the stencil, a mismatch at the codon 12 which lies within the AluI enzyme binding site and partially inhibits its activity. The mismatch also lowers the melting temperature of the stencil-mutant K-RAS double helix as compared to stencil–wild-type duplex, so that only the latter is double stranded and selectively digested by AluI at elevated temperatures. The proposed method of stencil-aided mutation analysis (SAMA) based on selective pre-PCR elimination of wild-type sequences can be highly advantageous for detection of mutant K-RAS due to: (i) an enhanced sensitivity because of reduced competition with a great excess of normal K-RAS, and (ii) a decrease in a number of false-positive results from Taq polymerase errors. Application of SAMA for generalized detection of DNA mutations is discussed. 相似文献
74.
Alexei V. Lobanov Ivan A. Borisov Sherald H. Gordon Richard V. Greene Timothy D. Leathers Anatoly N. Reshetilov 《Biosensors & bioelectronics》2001,16(9-12):1001-1007
Although biosensors based on whole microbial cells have many advantages in terms of convenience, cost and durability, a major limitation of these sensors is often their inability to distinguish between different substrates of interest. This paper demonstrates that it is possible to use sensors entirely based upon whole microbial cells to selectively measure ethanol and glucose in mixtures. Amperometric sensors were constructed using immobilized cells of either Gluconobacter oxydans or Pichia methanolica. The bacterial cells of G. oxydans were sensitive to both substrates, while the yeast cells of P. methanolica oxidized only ethanol. Using chemometric principles of polynomial approximation, data from both of these sensors were processed to provide accurate estimates of glucose and ethanol over a concentration range of 1.0–8.0 mM (coefficients of determination, R2=0.99 for ethanol and 0.98 for glucose). When data were processed using an artificial neural network, glucose and ethanol were accurately estimated over a range of 1.0–10.0 mM (R2=0.99 for both substrates). The described methodology extends the sphere of utility for microbial sensors. 相似文献
75.
Konstantin B Shumaev Andrey A Gubkin Vladimir A Serezhenkov Irina I Lobysheva Olga V Kosmachevskaya Enno K Ruuge Vadim Z Lankin Alexey F Topunov Anatoly F Vanin 《Nitric oxide》2008,18(1):37-46
Destructive effect of superoxide anions O2- derived from KO(2) or xanthine-xanthine oxidase system on dinitrosyl-iron complexes bound with bovine albumin or methemoglobin (DNIC-BSA or DNIC-MetHb) was demonstrated. The sensitivity of DNIC-BSA synthesized by the addition of DNIC with cysteine, thiosulfate or phosphate (DNIC-BSA-1, DNIC-BSA-2 or DNIC-BSA-3, respectively) to destructive action of O2- decreased in row: DNIC-BSA-1>DNIC-BSA-3>DNIC-BSA-2. The estimated rate constant for the reaction between O2- and DNIC-BSA-3 was equal to approximately 10(7)M(-1)s(-1). However, hydrogen peroxide and tert-butyl hydrogenperoxide (t-BOOH) did not induce any noticeable degradation of DNIC-BSA-3 even when used at concentrations exceeding by one order of magnitude those of the complex. As to their action on DNIC-MetHb both hydrogen peroxide and t-BOOH-induced rapid degradation of the complex. Both agents could induce the process due to the effect of alkylperoxyl or protein-derived free radicals formed at the interaction of the agents with ferri-heme groups of MetHb. Peroxynitrite (ONOO(-)) could also initiate protein-bound DNIC degradation more efficiently in the reaction with DNIC-BSA-3. Higher resistance of DNIC-MetHb to peroxynitrite was most probably due to the protective action of heme groups on ONOO(-). However, the analysis allows to suggest that the interaction of protein-bound DNICs with O2- is the only factor responsible for the degradation of the complexes in cells and tissues. 相似文献
76.
Inhibition of yes‐associated protein suppresses brain metastasis of human lung adenocarcinoma in a murine model 下载免费PDF全文
Ping‐Chih Hsu Jinbai Miao Zhen Huang Yi‐Lin Yang Zhidong Xu Joanna You Yuyuan Dai Che‐Chung Yeh Geraldine Chan Shu Liu Anatoly Urisman Cheng‐Ta Yang David M. Jablons Liang You 《Journal of cellular and molecular medicine》2018,22(6):3073-3085
Yes‐associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030‐BrM3(K‐rasG12C mutation) and PC9‐BrM3 (EGFRΔexon19 mutation) had a significantly decreased p‐YAP(S127)/YAP ratio compared to parental H2030 (K‐rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < .05). H2030‐BrM3 cells had significantly increased YAP mRNA and expression of Hippo downstream genes CTGF and CYR61 compared to parental H2030 cells (P < .05). Inhibition of YAP by short hairpin RNA (shRNA) and small interfering RNA (siRNA) significantly decreased mRNA expression in downstream genes CTGF and CYR61 in H2030‐BrM3 cells (P < .05). In addition, inhibiting YAP by YAP shRNA significantly decreased migration and invasion abilities of H2030‐BrM3 cells (P < .05). We are first to show that mice inoculated with YAP shRNA‐transfected H2030‐BrM3 cells had significantly decreased metastatic tumour burden and survived longer than control mice (P < .05). Collectively, our results suggest that YAP plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of YAP by shRNA suppresses H2030‐BrM3 cell brain metastasis in a murine model. 相似文献
77.
Elena Berezhnaya Maria Neginskaya Anatoly B. Uzdensky Andrey Y. Abramov 《Molecular neurobiology》2018,55(1):90-95
Photodynamic therapy is selective destruction of cells stained with a photosensitizer upon irradiation with light at a specific wavelength in the presence of oxygen. Cell death upon photodynamic treatment is known to occur mainly due to free radical production and subsequent development of oxidative stress. During photodynamic therapy of brain tumors, healthy cells are also damaged; considering this, it is important to investigate the effect of the treatment on normal neurons and glia. We employed live-cell imaging technique to investigate the cellular mechanism of photodynamic action of radachlorin (200 nM) on neurons and astrocytes in primary rat cell culture. We found that the photodynamic effect of radachlorin increases production of reactive oxygen species measured by dihydroethidium and significantly decrease mitochondrial membrane potential. Mitochondrial depolarization was independent of opening of mitochondrial permeability transition pore and was insensitive to blocker of this pore cyclosporine A. However, irradiation of cells with radachlorin dramatically decreased NADH autofluorescence and also reduced mitochondrial NADH pool suggesting inhibition of mitochondrial respiration by limitation of substrate. This effect could be prevented by inhibition of poly (ADP-ribose) polymerase (PARP) with DPQ. Thus, irradiation of neurons and astrocytes in the presence of radachlorin leads to activation of PARP and decrease in NADH that leads to mitochondrial dysfunction. 相似文献
78.
Svetlana E Medvedeva Anatoly Boyandin Yuly Lankin Dmitry Kotov Emma Rodicheva Lyudmila Popova 《Luminescence》2005,20(2):90-96
The Institute of Biophysics SB RAS hosts and maintains a specialized collection of luminous bacteria (CCIBSO 836) containing over 700 strains isolated in various regions of the world's oceans. The culture collection is a source of lux genes and biologically active substances. The wide application of bioluminescence in medicine and ecology has given importance to analysing information on the structure and functioning of bioluminescence systems in natural and transgenic microorganisms, as well as on their features that are closely interrelated with bioluminescence. The aims of our BIOLUMBASE database are: gathering information on microorganisms with lux genes, their analysis and free access, and distribution of this data throughout the global network. The database includes two sections, natural and transgenic luminous microorganisms, and is updated by our own experimental results, the published literature and internet resources. For the future, a publicly available internet site for BIOLUMBASE is planned. This will list the strains and provide comprehensive information on the properties and functions of luminous bacteria, the mechanisms of regulation of bioluminescence systems, constructs with lux genes, and applications of bioluminescence in microbiology, ecology, medicine and biotechnology. It is noteworthy that this database will also be useful for evaluation of biological hazards of transgenic strains. Users will be able to carry out bibliographic and strain searches starting from any feature of interest. 相似文献
79.
Yvonne Lundberg Giwercman Andrej Nikoshkov Kristina Lindsten Birgitta Byström Å. Pousette Alexander V. Chibalin Sivonne Arvidsson Anatoly Tiulpakov Tatiana V. Semitcheva Valentina Peterkova Kerstin Hagenfeldt E. Martin Ritzén A. Wedell 《Human genetics》1998,103(4):529-431
Five mutations in the ligand-binding domain of the androgen receptor gene were identified in patients with complete (A765T,
C784Y, R831X and M895T) or partial (R840G) androgen insensitivity. A765T and R831X have been reported previously whereas the
other three mutations are novel. Receptors carrying these mutations were transiently expressed in COS-1 cells, and androgen
binding and capacity to transactivate an androgen-responsive reporter gene were assayed. C784Y led to abolished androgen
binding and transactivating capacity, R840G and M895T showed reduced specific binding and partial transactivation. The in
vitro functions of the R840G and M895T mutants were improved with supraphysiological concentrations of steroid.
Received: 10 June 1998 / Accepted: 10 September 1998 相似文献
80.
Nikolay I. Zhurilo Mikhail V. Chudinov Andrey V. Matveev Olga S. Smirnova Irina D. Konstantinova Anatoly I. Miroshnikov Alexander N. Prutkov Lyubov E. Grebenkina Natalya V. Pulkova Vitaly I. Shvets 《Bioorganic & medicinal chemistry letters》2018,28(1):11-14
The novel isosteric ribavirin analogues were synthesized by two different ways. Some of them showed significant antiviral action against hepatitis C virus (HCV), herpes simplex (HCV-1) and influenza A virus comparable to that of ribavirin itself. The data obtained confirm the proposed theory of the ribavirin possible antiviral activity mechanism related with bioisosterism. 相似文献