全文获取类型
收费全文 | 15526篇 |
免费 | 1368篇 |
国内免费 | 13篇 |
出版年
2022年 | 96篇 |
2021年 | 196篇 |
2020年 | 127篇 |
2019年 | 164篇 |
2018年 | 229篇 |
2017年 | 170篇 |
2016年 | 329篇 |
2015年 | 545篇 |
2014年 | 628篇 |
2013年 | 764篇 |
2012年 | 1022篇 |
2011年 | 976篇 |
2010年 | 644篇 |
2009年 | 591篇 |
2008年 | 897篇 |
2007年 | 833篇 |
2006年 | 788篇 |
2005年 | 828篇 |
2004年 | 804篇 |
2003年 | 777篇 |
2002年 | 776篇 |
2001年 | 214篇 |
2000年 | 149篇 |
1999年 | 236篇 |
1998年 | 223篇 |
1997年 | 149篇 |
1996年 | 152篇 |
1995年 | 146篇 |
1994年 | 144篇 |
1993年 | 130篇 |
1992年 | 150篇 |
1991年 | 118篇 |
1990年 | 133篇 |
1989年 | 116篇 |
1988年 | 124篇 |
1987年 | 120篇 |
1986年 | 116篇 |
1985年 | 137篇 |
1984年 | 155篇 |
1983年 | 127篇 |
1982年 | 146篇 |
1981年 | 154篇 |
1980年 | 158篇 |
1979年 | 106篇 |
1978年 | 105篇 |
1977年 | 95篇 |
1976年 | 82篇 |
1975年 | 85篇 |
1974年 | 110篇 |
1973年 | 89篇 |
排序方式: 共有10000条查询结果,搜索用时 187 毫秒
991.
992.
A series of N-protected peptide alcohols were synthesized using amino alcohols with unprotected hydroxy groups as amino components by the catalysis of subtilisin or alpha-chymotrypsin in organic solvents. N-protected aromatic amino acid esters were more suitable as acyl donors for subtilisin. The influences of different N-protecting groups, organic solvents, and content of water on synthesis of N-protected peptide alcohols were systematically studied. 相似文献
993.
994.
Kumar V Carlson JE Ohgi KA Edwards TA Rose DW Escalante CR Rosenfeld MG Aggarwal AK 《Molecular cell》2002,9(4):857-869
The Lcd1p/Mec1p complex is crucial for normal S phase progression and for signaling DNA damage. We show that Lcd1p/Ddc2p and Mec1p in cell extracts bind to DNA ends. Although Lcd1p binds DNA independently of Mec1p, recruitment of Mec1p to DNA requires Lcd1p. DNA binding by Lcd1p is also independent of Rad9p, Rad17p, and Rad24p. Recombinant Lcd1p binds DNA, and this is impaired by Lcd1p mutations that abrogate its in vivo functions. Furthermore, Mec1p is recruited to cdc13-induced DNA damage and HO endonuclease-induced double-strand breaks in vivo. This requires Lcd1p, and recruitment of Lcd1p/Mec1p to cdc13-induced damage is abolished by Lcd1p mutations that abrogate its in vivo functions. Recruitment of Lcd1p to these lesions is independent of Mec1p and Rad9p/Rad24p. Thus, recruitment of Mec1p to DNA lesions by Lcd1p is crucial for the DNA damage response. 相似文献
995.
996.
P-glycoprotein (P-gp) is a drug transporter which pumps toxic hydrophobic compounds out of cells, conferring mutidrug resistance. P-gp is predicted to consist of 12 transmembrane alpha-helices and there is a strong body of experimental support for this model. However, a number of studies, including those on P-gp expressed in E. coli, have reported topologies with fewer than 12 transmembrane alpha-helices, leading to the hypothesis that the transmembrane topology of the protein changes during function. It is well established that P-gp undergoes conformational changes during its transport cycle and it has been recently shown that these changes are large in magnitude and could, potentially, reflect a changing transmembrane topology. One therefore, reassessed the transmembrane topology of P-gp expressed in E. coli and compared it directly with the topology of the protein expressed in mammalian cells. It was clear that the transmembrane topology of the protein was different in the different cell types and that the misfolding of P-gp in E. coli was due to the misrecognition of multiple P-gp sequences as topogenic signals. Thus, the alternative transmembrane topologies reported for P-gp in E. coli are artefacts of the heterologous expression system used, and models based on such data in which the transmembrane topology changes during drug transport are unlikely to be correct. Instead, the large conformational changes observed during the transport cycle are more likely due to changes in alpha-helix packing. 相似文献
997.
Hori H Nagasawa H Ishibashi M Uto Y Hirata A Saijo K Ohkura K Kirk KL Uehara Y 《Bioorganic & medicinal chemistry》2002,10(10):3257-3265
A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine kinase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. 相似文献
998.
Elucidation of the ultrastructural organization of actin networks is crucial for understanding the molecular mechanisms underlying actin-based motility. Results obtained from cytoskeletons and actin comets prepared by the critical-point procedure, followed by rotary shadowing, support recent models incorporating actin filament branching as a main feature of lamellipodia and pathogen propulsion. Since actin branches were not evident in earlier images obtained by negative staining, we explored how these differences arise. Accordingly, we have followed the structural fate of dense networks of pure actin filaments subjected to steps of the critical-point drying protocol. The filament networks have been visualized in parallel by both cryo-electron microscopy and negative staining. Our results demonstrate the selective creation of branches and other artificial structures in pure F-actin networks by the critical-point procedure and challenge the reliability of this method for preserving the detailed organization of actin assemblies that drive motility. 相似文献
999.
Scd5p and clathrin function are important for cortical actin organization,endocytosis, and localization of sla2p in yeast
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Henry KR D'Hondt K Chang J Newpher T Huang K Hudson RT Riezman H Lemmon SK 《Molecular biology of the cell》2002,13(8):2607-2625
SCD5 was identified as a multicopy suppressor of clathrin HC-deficient yeast. SCD5 is essential, but an scd5-Delta338 mutant, expressing Scd5p with a C-terminal truncation of 338 amino acids, is temperature sensitive for growth. Further studies here demonstrate that scd5-Delta338 affects receptor-mediated and fluid-phase endocytosis and normal actin organization. The scd5-Delta338 mutant contains larger and depolarized cortical actin patches and a prevalence of G-actin bars. scd5-Delta338 also displays synthetic negative genetic interactions with mutations in several other proteins important for cortical actin organization and endocytosis. Moreover, Scd5p colocalizes with cortical actin. Analysis has revealed that clathrin-deficient yeast also have a major defect in cortical actin organization and accumulate G-actin. Overexpression of SCD5 partially suppresses the actin defect of clathrin mutants, whereas combining scd5-Delta338 with a clathrin mutation exacerbates the actin and endocytic phenotypes. Both Scd5p and yeast clathrin physically associate with Sla2p, a homologue of the mammalian huntingtin interacting protein HIP1 and the related HIP1R. Furthermore, Sla2p localization at the cell cortex is dependent on Scd5p and clathrin function. Therefore, Scd5p and clathrin are important for actin organization and endocytosis, and Sla2p may provide a critical link between clathrin and the actin cytoskeleton in yeast, similar to HIP1(R) in animal cells. 相似文献
1000.
The relationship of the heart rate deflection point to the ventilatory threshold in trained cyclists
Bodner ME Rhodes EC Martin AD Coutts KD 《Journal of strength and conditioning research / National Strength & Conditioning Association》2002,16(4):573-580
The purpose of this study was to assess the relationship of the heart rate deflection point (HRDP) to the ventilatory threshold (VT) in trained cyclists. Twenty-one endurance-trained cyclists (mean +/- SD: Vo(2)max = 67.6 +/- 4.7 ml x kg x min(-1)) completed a maximal cycle ergometer test of volitional fatigue using a ramped protocol. Ventilatory variables (Ve, Vo(2), Vco(2)) and power were measured online with averages reported every 20 seconds. Heart rate (HR) was recorded every 20 seconds using a Polar monitor. VT was calculated using the excess CO(2) elimination curve. The first derivative of a logistic growth curve fit to the HR-power data produced the HRDP. No significant differences (p > 0.01) existed between HR values at HRDP (171.7 +/- 9.6 b x min(-1)) and VT (169.8 +/- 9.9 b x min(-1)) or between Vo(2) values at HRDP (53.6 +/- 4.2 ml x kg x min(-1)) and VT (52.2 +/- 4.8 ml x kg x min(-1)). But power values at HRDP (318.7 +/- 30.7 W) were significantly different (p < 0.01) from those at VT (334.8 +/- 36.7 W). There were significant relationships between HRDP and VT for the physiological variables of HR (r = 0.92, p < 0.001), Vo(2) (r = 0.72, p < 0.001), and power (r = 0.77, p < 0.001). These findings indicate that HR and Vo(2) at HRDP are not significantly different from the values at VT in trained cyclists. HR values derived from HRDP may be used to set parameters for training intensity. Variability in the speed/power-HRDP relationship across detrained/trained states may be used to evaluate training programs. 相似文献