全文获取类型
收费全文 | 5125篇 |
免费 | 340篇 |
国内免费 | 2篇 |
出版年
2022年 | 19篇 |
2021年 | 66篇 |
2020年 | 30篇 |
2019年 | 49篇 |
2018年 | 61篇 |
2017年 | 66篇 |
2016年 | 88篇 |
2015年 | 158篇 |
2014年 | 173篇 |
2013年 | 299篇 |
2012年 | 293篇 |
2011年 | 277篇 |
2010年 | 190篇 |
2009年 | 203篇 |
2008年 | 275篇 |
2007年 | 282篇 |
2006年 | 279篇 |
2005年 | 278篇 |
2004年 | 249篇 |
2003年 | 245篇 |
2002年 | 259篇 |
2001年 | 124篇 |
2000年 | 131篇 |
1999年 | 127篇 |
1998年 | 72篇 |
1997年 | 57篇 |
1996年 | 51篇 |
1995年 | 43篇 |
1994年 | 28篇 |
1993年 | 46篇 |
1992年 | 76篇 |
1991年 | 84篇 |
1990年 | 84篇 |
1989年 | 73篇 |
1988年 | 65篇 |
1987年 | 57篇 |
1986年 | 58篇 |
1985年 | 56篇 |
1984年 | 41篇 |
1983年 | 41篇 |
1982年 | 43篇 |
1981年 | 27篇 |
1980年 | 20篇 |
1979年 | 24篇 |
1978年 | 23篇 |
1977年 | 24篇 |
1976年 | 16篇 |
1974年 | 25篇 |
1973年 | 22篇 |
1971年 | 12篇 |
排序方式: 共有5467条查询结果,搜索用时 15 毫秒
1.
Irreversible inactivation at high temperature of temperature-sensitive mutant tRNA Tyr in vivo 总被引:1,自引:0,他引:1
Y Nomura 《Nature: New biology》1973,242(114):12-14
2.
K Nomura H Imai T Koumura M Arai Y Nakagawa 《The Journal of biological chemistry》1999,274(41):29294-29302
Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a key enzyme in the protection of biomembranes exposed to oxidative stress. We investigated the role of mitochondrial PHGPx in apoptosis using RBL2H3 cells that overexpressed mitochondrial PHGPx (M15 cells), cells that overexpressed non-mitochondrial PHGPx (L9 cells), and control cells (S1 cells). The morphological changes and fragmentation of DNA associated with apoptosis occurred within 15 h in S1 and L9 cells upon exposure of cells to 2-deoxyglucose (2DG). The release of cytochrome c from mitochondria was observed in S1 cells after 4 h and was followed by the activation of caspase-3 within 6 h. Overexpression of mitochondrial PHGPx prevented the release of cytochrome c, the activation of caspase-3, and apoptosis, but non-mitochondrial PHGPx lacked the ability to prevent the induction of apoptosis by 2DG. An ability to protect cells from 2DG-induced apoptosis was abolished when the PHGPx activity of M15 cells was inhibited by diethylmalate, indicating that the resistance of M15 cells to apoptosis was indeed due to the overexpression of PHGPx in the mitochondria. The expression of members of the Bcl-2 family of proteins, such as Bcl-2, Bcl-xL, Bax, and Bad, was unchanged by the overexpression of PHGPx in cells. The levels of hydroperoxides, including hydrogen and lipid peroxide, in mitochondria isolated from S1 and L9 cells were significantly increased after the exposure to 2DG for 2 h, while the level of hydroperoxide in mitochondria isolated from M15 cells was lower than that in S1 and L9 cells. M15 cells were also resistant to apoptosis induced by etoposide, staurosporine, UV irradiation, cycloheximide, and actinomycin D, but not to apoptosis induced by Fas-specific antibodies, which induces apoptosis via a pathway distinct from the pathway initiated by 2DG. Our results suggest that hydroperoxide, produced in mitochondria, is a major factor in apoptosis and that mitochondrial PHGPx might play a critical role as an anti-apoptotic agent in mitochondrial death pathways. 相似文献
3.
Masaki Saito Hiroyuki Tanaka Masako Sasaki Hitoshi Kurose Norimichi Nakahata 《Cellular signalling》2010,22(1):41-46
The physiological role of the thromboxane A2 (TXA2) receptor expressed on glial cells remains unclear. We previously reported that 1321N1 human astrocytoma cells pretreated with dibutyryl cyclic AMP (dbcAMP) became swollen in response to U46619, a TXA2 analogue. In the present study, we examined the detailed mechanisms of TXA2 receptor-mediated cell swelling in 1321N1 cells. The cell swelling caused by U46619 was suppressed by expression of p115-RGS, an inhibitory peptide of Gα12/13 pathway and C3 toxin, an inhibitory protein for RhoA. The swelling was also inhibited by treatment with Y27632, a Rho kinase inhibitor and 5-(ethyl-N-isopropyl)amiloride (EIPA), a Na+/H+-exchanger inhibitor. Furthermore, cell swelling was suppressed by the pretreatment with aquaporin inhibitors mercury chloride or phloretin in a concentration-dependent manner, suggesting that aquaporins are involved in U46619-induced 1321N1 cell swelling. In fact, U46619 caused [3H]H2O influx into the cells, which was inhibited by p115-RGS, C3 toxin, EIPA, mercury chloride and phloretin. This is the first report that the TXA2 receptor mediates water influx through aquaporins in astrocytoma cells via TXA2 receptor-mediated activation of Gα12/13, Rho A, Rho kinase and Na+/H+-exchanger. 相似文献
4.
Induction of erythroid differentiation by cytoplast fusion in mouse erythroleukemia (Friend) cells 总被引:6,自引:0,他引:6
An intracellular activity, which is induced by dimethyl sulfoxide (DMSO) or hexamethylenebisacetamide (HMBA) and leads to erythroid differentiation in mouse Friend cells, was characterized by cell fusion between genetically marked intact cells and cytoplasts. For this, a procedure for rapid selection of cybrids was devised by sensitizing non-fused cells with oligomycin. We were able to demonstrate that cytoplasts derived from DMSO- (or HMBA)-treated cells trigger erythroid differentiation upon fusion with UV-irradiated cells. The activity in the cytoplasts remained only transiently and its induction was inhibited by biologically active phorbol esters or cycloheximide. The activity, however, was not induced in cytoplasts by directly treating them with DMSO (or HMBA). These results indicate that (1) the intracellular erythroid-inducing activity is located in cytoplasts, (2) it acts in trans and induces erythroid differentiation as a dominant factor and (3) its production requires de novo nuclear protein synthesis. The mechanisms of the induction of the intracellular activity and of how it triggers erythroid differentiation are discussed. 相似文献
5.
H Kobayashi A Inoue T Mikawa H Kuwayama Y Hotta T Masaki S Ebashi 《Journal of biochemistry》1992,112(6):786-791
Two proteins with myosin light chain kinase activity and electrophoretic molecular weights of 155,000 and 130,000 were each isolated from bovine stomach smooth muscle [Kuwayama, H., Suzuki, M., Koga, R., & Ebashi, S. (1988) J. Biochem. 104, 862-866]. The 155 kDa component showed a much higher superprecipitation-inducing activity than the 130 kDa component, when compared on the basis of equivalent myosin light chain kinase activity. In this study, we isolated a cDNA for the entire coding region of the 155 kDa protein. The deduced amino acid sequence revealed a high degree of similarity to those of chicken and rabbit smooth muscle myosin light chain kinases. Multiple motifs, such as three repeats of an immunoglobulin C2-like domain, a fibronectin type III domain, and unusual 20 repeats of 12 amino acids were detected in the sequence. Part of the amino-terminal sequence was similar to that of the actin- and calmodulin-binding domain of smooth muscle caldesmon. These observations suggest that the 155 kDa protein has additional functions other than its enzymatic activity. Two mRNAs of 6.0 and 2.6 kb in length in the bovine stomach smooth muscle RNAs were hybridized with cDNA probes. The 2.6-kb RNA probably encodes telokin, which is the carboxyl terminus of smooth muscle myosin light chain kinase. mRNAs with identical lengths were also detected in bovine aorta. 相似文献
6.
A Kuroiwa K Matsubara T Nagase N Nomura J K Seong A Ishikawa R V Anunciado K Tanaka T Yamagata J S Masangkay V B Dang T Namikawa Y Matsuda 《The Journal of heredity》2001,92(3):282-287
The direct R-banding fluorescence in situ hybridization (FISH) method was used to map 18S-28S ribosomal RNA genes and 10 human cDNA clones on the chromosomes of the musk shrew (Suncus murinus). The chromosomal locations of 18S-28S ribosomal RNA genes were examined in the five laboratory lines and wild animals captured in the Philippines and Vietnam, and the genes were found on chromosomes 5, 6, 9, and 13 with geographic variation. The comparative mapping of 10 cDNA clones of human chromosome 1 demonstrated that human chromosome 1 consisted of at least three segments homologous to Suncus chromosomes (chromosomes 7, 10, and 14). This approach with the direct R-banding FISH method is useful for constructing comparative maps between human and insectivore species and for explicating the process of chromosomal rearrangements during the evolution of mammals. 相似文献
7.
Inhibin activity in goat seminal plasma was measured by in vitro assay throughout successive 9 months and its relationship with the serum FSH, LH and testosterone concentrations was investigated. Total inhibin activity (TIA) in seminal plasma gradually increased from spring to summer, reduced in autumn (P<0.05) and recovered toward winter (P<0.05). Serum FSH and LH reached a peak in mid-summer (P<0.01) and returned to the low levels in autumn. Serum testosterone also increased in mid-summer and kept the high levels until the early winter (P<0.05). Some positive correlation was found in monthly levels between seminal TIA and serum FSH (r=0.305; P<0.05). Results suggest that the summer increase of inhibin activity in seminal plasma relates with the mid-summer rise of serum FSH levels in the male goat. 相似文献
8.
Phenylalanine Transport Across the Blood-Brain Barrier as Studied with the In Situ Brain Perfusion Technique 总被引:6,自引:5,他引:1
Seiji Momma Masaki Aoyagi Stanley I. Rapoport Quentin R. Smith 《Journal of neurochemistry》1987,48(4):1291-1300
Unidirectional L-phenylalanine transport into six brain regions of pentobarbital-anesthetized rats was studied using the in situ brain perfusion technique. This technique allows both accurate measurements of cerebrovascular amino acid transport and complete control of perfusate amino acid composition. L-Phenylalanine influx into the brain was sodium independent and could be described by a model with a saturable and a nonsaturable component. Best-fit values for the kinetic constants in the parietal cortex equaled 6.9 X 10(-4) mumol/s/g for Vmax, 0.011 mumol/ml for Km, and 1.8 X 10(-4) ml/s/g for KD during perfusion with fluid that did not contain competing amino acids. D-Phenylalanine competitively inhibited L-phenylalanine transport with a Ki approximately 10-fold greater than the Km for L-phenylalanine. There were no significant regional differences in Km, KD, or Ki, whereas Vmax was significantly greater in the cortical lobes than in the other brain regions. L-Phenylalanine influx during plasma perfusion was only 30% of that predicted in the absence of competing amino acids. Competitive inhibition increased the apparent Km during plasma perfusion by approximately 20-fold, to 0.21 mumol/ml. These data provide accurate new estimates of the kinetic constants that describe L-phenylalanine transport across the blood-brain barrier. In addition, they indicate that the cerebrovascular transfer site affinity (1/Km) for L-phenylalanine is three- to 12-fold greater than previously estimated in either awake or anesthetized animals. 相似文献
9.
Kinetics of Neutral Amino Acid Transport Across the Blood-Brain Barrier 总被引:20,自引:8,他引:12
Quentin R. Smith Seiji Momma Masaki Aoyagi Stanley I. Rapoport 《Journal of neurochemistry》1987,49(5):1651-1658
Neutral amino acid (NAA) transport across the blood-brain barrier was examined in pentobarbital-anesthetized rats with an in situ brain perfusion technique. Fourteen of 16 plasma NAAs showed measurable affinity for the cerebrovascular NAA transport system. Values of the transport constants (Vmax, Km, KD) were determined for seven large NAAs from saturation studies, whereas Km values for five small NAAs were estimated from inhibition studies. These data, together with our previous work, provide a complete set of constants for prediction of NAA influx from plasma. Among the NAAs, Vmax varied at least fivefold and Km varied approximately 700 fold. The apparent affinity (1/Km) of each NAA was related linearly (r = 0.910) to the octanol/water partition coefficient, a measure of NAA side-chain hydrophobicity. Predicted influx values from transport constants and average plasma concentrations agree well with values measured using plasma perfusate. These results provide accurate new estimates of the kinetic constants that determine NAA transport across the blood-brain barrier. Furthermore, they suggest that affinity of a L-alpha-amino acid for the transport system is determined primarily by side-chain hydrophobicity. 相似文献
10.
Mutagenicity of N4-aminocytidine and its derivatives in Chinese hamster lung V79 cells. Incorporation of N4-aminocytosine into cellular DNA 总被引:2,自引:0,他引:2
N4-Aminocytidine induced mutation to 6-thioguanine resistance in Chinese hamster lung V79 cells in culture. Previous studies with experimental systems of in vitro DNA synthesis and of phage and bacterial mutagenesis have shown that this nucleoside analog induces base-pair transitions through its incorporation into DNA, with its erroneous base-pairing property. Incorporation of exogenously added [5-3H]N4-aminocytidine into the DNA of V79 cells was in fact observed in the present study. N4-Aminodeoxycytidine was not mutagenic for the V79 cells. Several alkylated N4-aminocytidine derivatives were tested for their mutagenicity in this system. Those with an alkyl group on the N'-nitrogen of the hydrazino group at position 4 of N4-aminocytidine were mutagenic, but those having an alkyl on the N4-nitrogen were not. These results are consistent with those previously observed in the bacterial mutagenesis systems, and agree with a mechanism of mutation in which a tautomerization of N4-aminocytosine is the necessary step for causing the erroneous base pairing. 相似文献