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961.
Jia Li Chenghui Yan Yilong Wang Can Chen Haibo Yu Dan Liu Kai Huang Yaling Han 《Cell death & disease》2022,13(4)
Pathological cardiac hypertrophy is a process of abnormal remodeling of cardiomyocytes in response to pressure overload or other stress stimuli, resulting in myocardial injury, which is a major risk factor for heart failure, leading to increased morbidity and mortality. General control nonrepressed protein 5 (GCN5)/lysine acetyltransferase 2 A, a member of the histone acetyltransferase and lysine acetyltransferase families, regulates a variety of physiological and pathological events. However, the function of GCN5 in pathological cardiac hypertrophy remains unclear. This study aimed to explore the role of GCN5 in the development of pathological cardiac hypertrophy. GCN5 expression was increased in isolated neonatal rat cardiomyocytes (NRCMs) and mouse hearts of a hypertrophic mouse model. GCN5 overexpression aggravated the cardiac hypertrophy triggered by transverse aortic constriction surgery. In contrast, inhibition of GCN5 impairs the development of pathological cardiac hypertrophy. Similar results were obtained upon stimulation of NRCMs (having GCN5 overexpressed or knocked down) with phenylephrine. Mechanistically, our results indicate that GCN5 exacerbates cardiac hypertrophy via excessive activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Using a TAK1-specific inhibitor in rescue experiments confirmed that the activation of TAK1 is essential for GCN5-mediated cardiac hypertrophy. In summary, the current study elucidated the role of GCN5 in promotion of cardiac hypertrophy, thereby implying it to be a potential target for treatment.Subject terms: Heart failure, Cell signalling 相似文献
962.
963.
Antonia Piazzesi Yiru Wang Joshua Jackson Lena Wischhof Viktoria ZeislerDiehl Enzo Scifo Ina Oganezova Thorben Hoffmann Pablo Gmez Martín Fabio Bertan Chester J J Wrobel Frank C Schroeder Dan Ehninger Kristian Hndler Joachim L Schultze Lukas Schreiber Gerhild van EchtenDeckert Pierluigi Nicotera Daniele Bano 《EMBO reports》2022,23(5)
964.
965.
Manman Zhang Wenliang Gong Dianjun Zhang Ming Ji Binjie Chen Beina Chen Xinyu Li Yuefei Zhou Chengyi Dong Gehua Wen Xiaoni Zhan Xiafang Wu Lulu Cui Yuliang Feng Siman Wang Huiya Yuan Enyu Xu Maosheng Xia Alexei Verkhratsky Baoman Li 《Cell death & disease》2022,13(4)
Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience 相似文献
966.
Chao-Bo Zhang Li-Hua Chen Ya-Ping Liu Xiao-Dong Ji Xiu-Ping Liu 《Ecological Engineering》2010,36(1):19-26
In order to evaluate influences of roots on soil shear strength, a triaxial compression test was carried out to study the shear strength of plain soil samples and composites comprised of roots of Robinia pseucdoacacia and soil from the Loess Plateau in Northwest China. Roots were distributed in soil in three forms: vertical, horizontal, and vertical–horizontal (cross). All samples were tested under two different soil water contents. Test results showed that roots have more impacts on the soil cohesion than the friction angle. The presence of roots in soil substantially increased the soil shear strength. Among three root distribution forms, the reinforcing effect of vertical–horizontal (cross) root distribution was the most effective. Increase in soil water content directly induced a decline in soil cohesion of all test samples and resulted in a decrease in shear strength for both plain soil samples and soil–root composites. It was concluded that the triaxial compression test can be effectively used to study influences of roots on soil shear strength. 相似文献
967.
Ploug M Østergaard S Gårdsvoll H Kovalski K Holst-Hansen C Holm A Ossowski L Danø K 《Biochemistry》2001,40(40):12157-12168
The high-affinity interaction between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays an important role in pericellular plasminogen activation. Since proteolytic degradation of the extracellular matrix has an established role in tumor invasion and metastasis, the uPA-uPAR interaction represents a potential target for therapeutic intervention. By affinity maturation using combinatorial chemistry we have now developed and characterized a 9-mer, linear peptide antagonist of the uPA-uPAR interaction demonstrating specific, high-affinity binding to human uPAR (K(d) approximately 0.4 nM). Studies by surface plasmon resonance reveal that the off-rate for this receptor-peptide complex is comparable to that measured for the natural protein ligand, uPA. The functional epitope on human uPAR for this antagonist has been delineated by site-directed mutagenesis, and its assignment to loop 3 of uPAR domain III (Met(246), His(249), His(251), and Phe(256)) corroborates data previously obtained by photoaffinity labeling and provides a molecular explanation for the extreme selectivity observed for the antagonist toward human compared to mouse, monkey, and hamster uPAR. When human HEp-3 cancer cells were inoculated in the presence of this peptide antagonist, a specific inhibition of cancer cell intravasation was observed in a chicken chorioallantoic membrane assay. These data imply that design of small organic molecules mimicking the binding determinants of this 9-mer peptide antagonist may have a potential application in combination therapy for certain types of cancer. 相似文献
968.
Price JA Brewer CS Howard TD Fossey SC Sale MM Ji L Krolewski AS Bowden DW 《Genomics》1999,62(2):208-215
Several recent genetic studies have suggested linkage of Type 2 diabetes (non-insulin-dependent diabetes mellitus) susceptibility to a region of chromosome 20q12-q13.1. To facilitate the identification and cloning of a diabetes susceptibility gene(s) in this region, we have constructed correlated radiation hybrid and YAC/BAC contig physical maps of the region. A high-resolution radiation hybrid map encompassing 9.5 Mb between the PLC and the CEBPB genes was constructed using 68 markers: 25 polymorphic markers, 15 known genes, 21 ESTs, and 7 random genomic sequences. The physical order of the polymorphic markers within this radiation hybrid map is consistent with published genetic maps. A YAC/BAC contig that gives continuous coverage between PLC and CEBPB was also constructed. This contig was constructed from 24 YACs, 34 BACs, and 1 P1 phage clone onto which 71 markers were mapped: 23 polymorphic markers, 12 genes, 24 ESTs, and 12 random genomic sequences. The radiation hybrid map and YAC/BAC physical map enable precise mapping of newly identified transcribed sequences and polymorphic markers that will aid in linkage and linkage disequilibrium studies and facilitate identification and cloning of candidate Type 2 diabetes susceptibility genes residing in 20q12-q13.1. 相似文献
969.
Izaguirre G Aguirre L Ji P Aneskievich B Haimovich B 《The Journal of biological chemistry》1999,274(52):37012-37020
The integrin alpha(IIb)beta(3) mediates tyrosine phosphorylation of a 105-kDa protein (pp105) in activated platelets. We have partially purified a 105-kDa tyrosine-phosphorylated protein from platelets stimulated with phorbol 12-myristate 13-acetate and obtained the sequence of an internal 12-mer peptide derived from this protein. The sequence was identical to human alpha-actinin sequences deposited in the Swiss Protein Database. alpha-Actinin, a 105-kDa protein in platelets, was subsequently purified from activated platelets by four sequential chromatographic steps. Fractions were analyzed by Western blotting and probed with alpha-actinin and anti-phosphotyrosine antibodies. The distribution of alpha-actinin and pp105 overlapped throughout the purification. Furthermore, in the course of this purification, a 105-kDa tyrosine-phosphorylated protein was only detected in fractions that contained alpha-actinin. The purified alpha-actinin protein was immunoprecipitated with antibodies to phosphotyrosine in the absence but not in the presence of phenyl phosphate. alpha-Actinin resolved by two-dimensional gel electrophoresis of activated platelet lysates was recognized by the antibodies to phosphotyrosine, whereas pretreatment of the platelets with bisindolylmaleimide, a protein kinase C inhibitor that prevents tyrosine phosphorylation of pp105, inhibited the reactivity of the antibodies to phosphotyrosine with alpha-actinin. Taken together, these data demonstrate that a fraction of alpha-actinin is tyrosine-phosphorylated in activated platelets. 相似文献
970.
Evolution of Microsatellites in the Yeast Saccharomyces cerevisiae: Role of Length and Number of Repeated Units 总被引:4,自引:0,他引:4
The observed and expected frequencies of occurrence of microsatellites in the yeast Saccharomyces cerevisiae were investigated. In all cases, the observed frequencies exceeded the expected ones. In contrast to predictions by Messier
et al. (1996), there is no critical number of repeats beyond which the observed frequencies of microsatellites significantly
exceed the frequencies expected in a random DNA sequence of the same size. Rather, the degree of deviation from expectation
was found to be dependent on the length of the microsatellite. That is, a fourfold concatemeric repeat of 3 bp was found to
deviate from expectation as much as threefold concatemeric repeat of 4 bp, unlike the deviation of a fourfold concatemeric
repeat of 4 bp. These findings suggest that microsatellites evolve through strand-slippage events, rather than recombination
events. This, in turn, suggests that the chances of erroneous hybridizations leading to strand-slippage are length dependent.
Received: 1 June 1998 / Accepted: 16 September 1998 相似文献