全文获取类型
收费全文 | 102527篇 |
免费 | 7614篇 |
国内免费 | 3586篇 |
出版年
2024年 | 161篇 |
2023年 | 1542篇 |
2022年 | 2235篇 |
2021年 | 3385篇 |
2020年 | 3500篇 |
2019年 | 4677篇 |
2018年 | 4025篇 |
2017年 | 2879篇 |
2016年 | 2835篇 |
2015年 | 3610篇 |
2014年 | 6502篇 |
2013年 | 7806篇 |
2012年 | 4743篇 |
2011年 | 6139篇 |
2010年 | 4585篇 |
2009年 | 5234篇 |
2008年 | 5380篇 |
2007年 | 5354篇 |
2006年 | 4891篇 |
2005年 | 4249篇 |
2004年 | 3781篇 |
2003年 | 3023篇 |
2002年 | 2678篇 |
2001年 | 1808篇 |
2000年 | 1507篇 |
1999年 | 1379篇 |
1998年 | 1429篇 |
1997年 | 1198篇 |
1996年 | 1147篇 |
1995年 | 1092篇 |
1994年 | 1019篇 |
1993年 | 836篇 |
1992年 | 865篇 |
1991年 | 728篇 |
1990年 | 656篇 |
1989年 | 558篇 |
1988年 | 489篇 |
1987年 | 465篇 |
1986年 | 383篇 |
1985年 | 545篇 |
1984年 | 717篇 |
1983年 | 470篇 |
1982年 | 580篇 |
1981年 | 459篇 |
1980年 | 373篇 |
1979年 | 368篇 |
1978年 | 286篇 |
1977年 | 253篇 |
1976年 | 220篇 |
1973年 | 181篇 |
排序方式: 共有10000条查询结果,搜索用时 218 毫秒
891.
N. Hayashi H. Seino K. Irie M. Watanabe K. L. Clark K. Matsumoto T. Nishimoto 《Molecular & general genetics : MGG》1996,253(1-2):149-156
The Saccharomyces cerevisiae temperature-sensitive mutants srm1-1, mtr1-2 and prp20-1 carry alleles of a gene encoding a homolog of mammalian RCC1. In order to identify a protein interacting with RCC1, a series
of suppressors of the srm1-1 mutation were isolated as cold-sensitive mutants and one of the mutants, designated ded1-21, was found to be defective in the DED1 gene. The double mutant, srm1-1 ded1-21, could grow at 35° C, but not at 37° C. A revertant of srm1-1 ded1-21 that became able to grow at 37° C acquired another mutation in the SRM1 gene, indicating the tight relationship between SRM1 and DED1. In all the rcc1
- strains examined, the amount of mutated SRM1 proteins was reduced or not detectable at the nonpermissive temperature. While
mutated SRM1 protein was stabilized in all of the rcc1
- strains by the ded1-21 mutation, the ded1-21 mutation suppressed both srm1-1 and mtr1-2, but not the prp20-1 mutation, contrary to the previous finding that overproduction of the S. cerevisiae Ran homolog GSP1 suppresses prp20-1, but not srm1-1 or mtr1-2.
Received: 20 March 1996/Accepted: 1 July 1996 相似文献
892.
N. Bonnefoy M. Kermorgant G. Dujardin P. Brivet-Chevillotte 《Molecular & general genetics : MGG》1996,251(2):204-210
TheSaccharomyces cerevisiae geneABC1 is required for the correct functioning of thebc
1 complex of the mitochondrial respiratory chain. By functional complementation of aS. cerevisiae abc1
– mutant, we have cloned aSchizosaccharomyces pombe cDNA, whose predicted product is 50% identical to the Abc1 protein. Significant homology is also observed with bacterial, nematode, and even human amino acid sequences of unknown function, suggesting that the Abc1 protein is conserved through evolution. The cloned cDNA corresponds to a singleS. pombe geneabc1Sp, located on chromosome II, expression of which is not regulated by the carbon source. Inactivation of theabc1Sp gene by homologous gene replacement causes a respiratory deficiency which is efficiently rescued by the expression of theS. cerevisiae ABC1 gene. The inactivated strain shows a drastic decrease in thebc
1 complex activity, a decrease in cytochromeaa3 and a slow growth phenotype. To our knowledge, this is the first example of the inactivation of a respiratory gene inS. pombe. Our results highlight the fact thatS. pombe growth is highly dependent upon respiration, and thatS. pombe could represent a valuable model for studying nucleo-mitochondrial interactions in higher eukaryotes. 相似文献
893.
E. Leberer T. Leeuw D. Harcus D. Y. Thomas J. Chenevert I. Herskowitz 《Molecular & general genetics : MGG》1996,252(5):608-621
The pheromone signal in the yeastSaccharomyces cerevisiae is transmitted by the and subunits of the mating response G-protein. TheSTE20 gene, encoding a protein kinase required for pheromone signal transduction, has recently been identified in a genetic screen for high-gene-dosage suppressors of a partly defective G mutation. The same genetic screen identifiedBEM1, which encodes an SH3 domain protein required for polarized morphogenesis in response to pheromone, and a novel gene, designatedMDG1 (multicopy suppressor ofdefectiveG-protein). TheMDG1 gene was independently isolated in a search for multicopy suppressors of abem1 mutation. TheMDG1 gene encodes a predicted hydrophilic protein of 364 amino acids with a molecular weight of 41 kDa that has no homology with known proteins. A fusion of Mdg1p with the green fluorescent protein fromAequorea victoria localizes to the plasma membrane, suggesting that Mdg1p is an extrinsically bound membrane protein. Deletion ofMDG1 causes sterility in cells in which the wild-type G has been replaced by partly defective G derivatives but does not cause any other obvious phenotypes. The mating defect of cells deleted forSTE20 is partially suppressed by multiple copies ofBEM1 andCDC42, which encodes a small GTP-binding protein that binds to Ste20p and is necessary for the development of cell polarity. Elevated levels ofSTE20 andBEM1 are capable of suppressing a temperature-sensitive mutation inCDC42. This complex network of genetic interactions points to a role for Bem1p and Mdg1p in G-protein mediated signal transduction and indicates a functional linkage between components of the pheromone signalling pathway and regulators of cell polarity during yeast mating. 相似文献
894.
895.
N. Amrani M. -E. Dufour N. Bonneaud F. Lacroute 《Molecular & general genetics : MGG》1996,252(5):552-562
In a search for proteins associated with Rna15p in processing the 3 ends of messenger RNAs, we have looked for suppressors that correct, even partially, the thermosensitive growth defect of therna15-2 mutant. Mutations in a single locus that we namedSSM5, were able to suppress both the thermosensitivity of cell growth and the mRNA 3 processing defect associated with therna15-2 mutation, but only slightly alleviated the thermosensitive growth defect of anrna14-1 mutant. Thessm5-1 mutant is sensitive to hydroxyurea at 37° C, a drug that inhibits DNA synthesis. By screening for complementation of the hydroxyurea-sensitive phenotype we cloned the corresponding wild-type gene and found that it corresponds to the essential geneSTS1 (also namedDBF8). Sts1p has an apparent molecular weight of 30 kDa and was confirmed to be a cytosolic protein by immunofluorescence analysis. Western blot analysis indicates that the thermosensitive mutant strainsrna15-2, rna14-1 andpap1-1 present a very low level of the Rna15p at 37° C. Thessm5-1 mutation restores the level of Rna15p in therna15-2 ssm5-1 double mutant. Use of the two-hybrid system suggests that Sts1p does not interact directly with Rna15p, but may be active as a homodimer. The present data suggest that Sts1p may play a role in the transport of Rna15p from the cytoplasm to the nucleus. 相似文献
896.
Accumulation of mitochondrial DNA deletions in myotubes cultured from muscles of patients with mitochondrial myopathies 总被引:1,自引:0,他引:1
J.-M. Collombet G. Mandon R. Dumoulin B. Mousson G. Stepien 《Molecular & general genetics : MGG》1996,253(1-2):182-188
Myoblast cultures were established from muscle biopsies of two patients harboring heteroplasmic mitochondrial (mt) DNA deletions.
The accumulation kinetics of the deleted mtDNA was followed during myoblast to myotube differentiation. The percent- age of
deleted mtDNA was determined by quantitative PCR in myoblasts, myotubes, and muscle biopsies. The deleted form accounted for
65% of the mtDNA present in a muscle biopsy from a patient harboring a 5.6-kb deletion. The percentage of deleted mtDNA was
1.2% in myoblasts and increased progressively after differentiation, up to 12% at 21 days after the commitment time. In a
second patient harboring a 2.8-kb deletion, the percentage of deleted mtDNA increased much more slowly: from 0.07% in myoblasts
to 0.21% after 22 days of differentiation, as compared with 45% in the muscle biopsy. Thus, a three- and ten-fold increase,
respectively, in the fraction of deleted mtDNA occurred during the differentiation of myoblasts to myotubes from the two patients.
The faster accumulation of deleted mtDNA in the first patient’s cells was linked to an earlier myoblast to myotube differentiation,
suggesting that the level of deleted mtDNA is inversely related to the rate of cell proliferation.
Received: 16 April 1996/Accepted: 29 July 1996 相似文献
897.
J. Tougaard 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1996,178(5):669-677
The temporal integration of the A1 auditory receptor of two species of noctuid moths (Lepidoptera, Noctuidae) was investigated. Tympanal nerve spikes were recorded while stimulating the ear with broad band clicks. Thresholds were measured for single clicks, pairs of clicks with a separation of 1–20 ms, and trains of up to 8 clicks at separations of 1–2 ms. The average threshold for single clicks was 52.9 dB peSPL (SD 1.7 dB, n = 40) for Noctua pronuba and 50.1 dB peSPL (SD 4.0 dB, n = 27) for Spodoptera littoralis. The thresholds for double clicks with a 1 ms separation were lower than the thresholds for single clicks. The difference decreased as the separation between the clicks was increased. The results were fully consistent with an energy detector model (a leaky integrator with an exponential decay) with a time constant of about 4 ms.The results are compared to previously published results with pure tone intensity/duration trading. A common underlying mechanism is suggested, based on the passive electric properties of the receptor cell membrane.It is suggested, that the time constant revealed in the present study characterizes auditory receptors in general, and is related to the short time constants in vertebrate audition.Abbreviations
peSPL
peak equivalent sound pressure level
-
SD
standard deviation
-
time constant 相似文献
898.
Koji Tamada Mamoru Harada Tadao Okamoto Mitsuhiro Takenoyama Osamu Ito Goro Matsuzaki Kikuo Nomoto 《Cancer immunology, immunotherapy : CII》1996,41(6):339-347
In order to expand tumor-infiltrating lymphocytes (TIL) efficiently and in order to use them for immunotherapy, we utilized lipopolysaccharide-activated B cells (LPS blasts) as costimulatory-signal-providing cells in an in vitro culture system. TIL, prepared from subcutaneously inoculated B16 melanoma, failed to expand when cultured with anti-CD3 monoclonal antibody (mAb) alone followed by a low dose of interleukin(IL)-2. In contrast, such TIL did expand efficiently in culture with both anti-CD3 mAb and LPS blasts followed by culture with IL-2. These findings suggest that the presence of LPS blasts in the initial culture was essential for the cell expansion. The expansion of TIL was partially blocked by the addition of CTLA4 Ig, which is an inhibitor of costimulatory molecules such as CD80 and CD86, and was almost blocked by the addition of anti-(Fc receptor II)mAb. These findings thus indicate that such molecules, in conjunction with the receptor on the LPS blasts, participate in the efficient expansion of TIL. The B16-derived TIL, which expanded in our culture system, were predominantly CD8+T cells and showed a higher level of cytolytic activity against B16 melanoma than either lymphokine-activated killer cells or TIL cultured with a high dose of IL-2. In addition, the in vitro expanded B16-derived TIL produced interferon , but not IL-4, in response to B16 melanoma. What is more important, the adoptive transfer of such TIL had a significant antitumor effect against pulmonary metastasis in B16 melanoma, even without the concurrent administration of IL-2. Collectively, our results thus indicate the therapeutic efficacy of the protocol presented here for antitumor immunotherapy with TIL.This work was supported in part by a grant from the Ministry of Education, Science and Culture 相似文献
899.
B. Kodadová 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1996,179(3):301-310
The ability of pheromone receptor cells of male Antheraea polyphemus (Saturniidae) to resolve stimulus pulses was determined at different temperatures (8°, 18°, 28°C). The cells were stimulated by repeated 20-ms puffs of the pheromone components (E, Z)-6, 11-hexadecadienyl acetate and (E, Z)-6,11-hexadecadienal. At higher temperatures, higher frequencies of stimulus pulses were resolved by the nerve-impulse response: about 1.25 pulses per second at 8°C, 2.5 pulses/s at 18°C and 5 pulses/s at 28°C. The decreased ability of receptor cells to resolve stimulus pulses at low temperatures may reduce the male moth's chance of reaching the pheromone source. The peak nerve-impulse frequency increased whereas the duration of nerve-impulse responses to single stimulus pulses decreased at higher temperatures. At a given temperature and stimulus intensity the peak nerveimpulse frequency decreased with shorter intervals between the stimulus pulses, but the duration of the responses remained almost constant. The time needed for recovery from adaptation caused by a single stimulus pulse was longer at lower temperatures. The aldehyde receptor cell recovered more quickly than the acetate cell. At low stimulus concentration, the resolution ability of the acetate cell was strongly decreased, whereas in the aldehyde cell it was only slightly impaired. 相似文献
900.
丝裂素活化蛋白激酶参与内皮素刺激的兔主动脉平滑肌细胞增生 总被引:11,自引:1,他引:10
内皮素(endothelin,ET)是已知的体内活性最强的缩血管物质,其缩血管作用由G蛋白偶联受体所介导。但ET强大的促血管平滑肌细胞(VSMC)增生效应的机理尚未完全阐明。本研究选用培养的兔胸主动脉VSMC,探讨丝裂素活化蛋白激酶(MAPK)在ET促细胞增生中的作用。结果表明:ET-1呈时间和浓度依赖性地促进细胞摄取 ̄3H-TdR和激活MAPK,此作用可被蛋白激酶C(proteinkinaseC,PKC)抑制剂Staurosporine(STP),H-7和ET_A受体拮抗剂BQ123所抑制,但不被酪氨酸激酶抑制剂HerbimycinA(Herb)所抑制,用PKC激动剂PMA(Phorbolmyristateacetate)预处理VSMC,使其PKC活性下调,可显著减弱ET-1对MAPK的激活能力。本结果提示:(1)MAPK参与ET-1所致的VSMC增生;(2)ET-1促细胞增生与激活MAPK的作用是由ET_A受体和PKC介导的。 相似文献