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51.
Myung-Hwa Kim Hee-Eun Roh Min-Nyung Lee Man-Wook Hur 《Cellular physiology and biochemistry》2007,20(6):703-714
In this age of massive genetic and protein information, a fast and reliable method of studying in vivo protein-protein interactions is necessary. We have developed a novel system that can overcome limitations of existing assay methods. This new method adopts two existing systems for fast analysis of diverse protein-protein interactions. For rapid, large-scale cloning, we adopted the Gateway system and developed novel destination vectors containing YFP N-terminus (YN) or YFP C-terminus (YC) to visualize protein-protein interactions in vivo using bimolecular fluorescence complementation (BiFC). Using this system, we investigated molecular interactions among the three POZ-domain regulatory proteins mAPM-1, LRF, KLHL10 that belong to a subgroup of human POZ-domain proteins, and showed that the POZ-domains of mAPM-1, LRF and KLHL10 could form both homodimers and heterodimers. This new method is a highly efficient, sensitive and specific assay method for protein-protein interaction in vivo. 相似文献
52.
Jason D. Roh Nicholas Houstis Andy Yu Bliss Chang Ashish Yeri Haobo Li Ryan Hobson Carolin Lerchenmüller Ana Vujic Vinita Chaudhari Federico Damilano Colin Platt Daniel Zlotoff Richard T. Lee Ravi Shah Michael Jerosch‐Herold Anthony Rosenzweig 《Aging cell》2020,19(6)
Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age‐related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24–30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age‐related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF. 相似文献
53.
ChanKyu Kang Robert W. Ashurst Jae-Jin Shim Yun Suk Huh Changhyun Roh 《Bioprocess and biosystems engineering》2014,37(10):1997-2004
Here, we present a simple method for controlling the density of Au nanoparticles (Au NPs) on a modified silicon substrate, by destabilizing the colloidal Au NPs with 3-mercaptopropyltrimethoxylsilane (3-MPTMS) for microelectromechanical-system-based applications to reduce tribological issues. A silicon surface was pretreated with a 3-MPTMS solution, immediately after which thiolated Au NPs were added to it, resulting in their uniform deposition on the silicon substrate. Without any material property change of the colloidal Au NPs, we observed the formation of large clusters Au NPs on the modified silicon surface. Analysis by scanning electron microscopy with energy dispersive X-ray spectroscopy indicated that the addition of 3-MPTMS resulted in an alternation of the chemical characteristics of the solution. Atomic force microscopy imaging supported the notion that silicon surface modification is the most important factor on tribological properties of materials along with ligand-modified Au NPs. The density of Au NPs on a silicon surface was significantly dependent on several factors, including the concentration of colloidal Au NPs, deposition time, and concentration of 3-MPTMS solution, while temperature range which was used throughout experiment was determined to have no significant effect. A relatively high density of Au NPs forms on the silicon surface as the concentrations of Au NPs and 3-MPTMS are increased. In addition, the maximum deposition of Au NPs on silicon wafer was observed at 3 h, while the effects of temperature variation were minimal. 相似文献
54.
Kim N Yoo JC Han JY Hwang EM Kim YS Jeong EY Sun CH Yi GS Roh GS Kim HJ Kang SS Cho GJ Park JY Choi WS 《Journal of cellular physiology》2012,227(3):1157-1167
Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule. 相似文献
55.
56.
Milescu M Vobecky J Roh SH Kim SH Jung HJ Kim JI Swartz KJ 《The Journal of general physiology》2007,130(5):497-511
Voltage-activated ion channels are essential for electrical signaling, yet the mechanism of voltage sensing remains under intense investigation. The voltage-sensor paddle is a crucial structural motif in voltage-activated potassium (K(v)) channels that has been proposed to move at the protein-lipid interface in response to changes in membrane voltage. Here we explore whether tarantula toxins like hanatoxin and SGTx1 inhibit K(v) channels by interacting with paddle motifs within the membrane. We find that these toxins can partition into membranes under physiologically relevant conditions, but that the toxin-membrane interaction is not sufficient to inhibit K(v) channels. From mutagenesis studies we identify regions of the toxin involved in binding to the paddle motif, and those important for interacting with membranes. Modification of membranes with sphingomyelinase D dramatically alters the stability of the toxin-channel complex, suggesting that tarantula toxins interact with paddle motifs within the membrane and that they are sensitive detectors of lipid-channel interactions. 相似文献
57.
DNA-methyltransferase-3B (DNMT3b) plays an important role in the generation of aberrant methylation in carcinogenesis. DNMT3b SNP has been associated with susceptibility to lung, head, neck, and breast cancer, but its association with the development
of colon cancer has not been reported. We investigated the relationship between the 39179GT polymorphism in the DNMT3b gene, which is involved in de novo methylation and is associated with the risk of adenocarcinoma of the colon in Koreans.
The DNMT3b 39179GT genotypes were determined by a PCR-RFLP method in 248 adenocarcinomas of colon cancer patients and in 248 healthy
controls matched as to age and sex. When stratified by sex and age, a significantly reduced risk of the combined GT and GG
genotypes was observed in younger patients (<59, adjusted OR = 0.255, 95% CI = 0.133–0.489) and in male patients (adjusted
OR = 0.383, 95% CI = 0.225–0.652). The DNMT3b 39179GT polymorphism may be a genetic determinant of adenocarcinoma of the colon, especially in younger Korean men. 相似文献
58.
Mehta M Hanumanthaiah CS Betala PA Zhang H Roh S Buttner W Penrose WR Stetter JR Pérez-Luna VH 《Biosensors & bioelectronics》2007,23(5):728-734
An integrated array of micron-dimension capacitors, originally developed for biometric applications (fingerprint identification), was engineered for detection of biological agents such as proteins and bacteria. This device consists of an array of 93,184 (256 x 364) individual capacitor-based sensing elements located underneath a thin (0.8 microm) layer of glass. This glass layer can be functionalized with organosilane-based monolayers to provide groups amenable for the immobilization of bioreceptors such as antibodies, enzymes, peptides, aptamers, and nucleotides. Upon functionalization with antibodies and in conjunction with signal amplification schemes that result in perturbation of the dielectric constant around the captured antigens, this system can be used as a detector of biological agents. Two signal amplification schemes were tested in this work: one consisted of 4 microm diameter latex immunobeads and a second one was based on colloidal gold catalyzed reduction of silver. These signal amplification approaches were demonstrated and show that this system is capable of specific detection of bacteria (Escherichia coli) and proteins (ovalbumin). The present work shows proof-of-principle demonstration that a simple fingerprint detector based on feedback capacitance measurements can be implemented as a biosensor. The approach presented could be easily expanded to simultaneously test for a large number of analytes and multiple samples given that this device has a large number of detectors. The device and required instrumentation is highly portable and does not require expensive and bulky instrumentation because it relies purely on electronic detection. 相似文献
59.
Thanigaimalai P Lee KC Sharma VK Joo C Cho WJ Roh E Kim Y Jung SH 《Bioorganic & medicinal chemistry letters》2011,21(22):6824-6828
Effect of a series of 1-phenylthioureas 1a-k and 1,3-disubstituted thioureas 2a-k were evaluated against melanin formation in melanoma B16 cell line and mushroom tyrosinase. Inhibitory activity of tyrosinase of 1-phenylthioureas 1a-k is parallel to their melanogenic inhibition. Thus, the melanogenic inhibition in melanoma B16 cells of 1-phenylthioureas could be the result of inhibition of tyrosinase. However, 1,3-diaryl or 1-phenyl-3-alkylthioureas, 2a-k, appears as melanogenic inhibitor without inhibition of tyrosinase. The molecular docking study of 1e and 2b to binding pocket of tyrosinase provided convincing explanation regarding the necessity of direct connection of planar phenyl to thiourea unit without N'-substitution of phenylthioureas 1 as tyrosinase inhibitor and 2 as non-tyrosinase inhibitor. 相似文献
60.
BORIS is a member of the cancer-testis gene family that comprises genes normally expressed only in testis but abnormally activated in different malignancies. In this study, we examined the relation between BORIS expression and gastric cancer, which is the most common cancer in Korea. Abnormal BORIS expression in the patient's gastric cancer tissues was observed. We checked the methylation status of the gene in gastric cancer tissue, because the regulation by methylation in its CpG islands is well known for BORIS. However, there was no correlation between the methylation status and gene expression. Then, we focused on the minisatellites (variable number of tandem repeats) of BORIS as another possible regulator for this abnormal expression. Previously, we reported the characterization of BORIS-MS2 and determined the frequency of alleles in cancer patients. A case-control study was performed using DNA from 774 controls and 496 patients with gastric cancer. There was no significant difference observed in the overall distribution of minisatellite alleles. These results suggest that additional different regulators for the abnormal BORIS expression in gastric cancer may exist. Additionally, we performed a segregation analysis of BORIS-MS2 with genomic DNA obtained from two generations of five families and from three generations of two families. BORIS-MS2 alleles were transmitted through meiosis following Mendelian inheritance, which suggests that this polymorphic minisatellite could be a useful marker for paternity mapping and DNA fingerprinting. 相似文献