全文获取类型
收费全文 | 5675篇 |
免费 | 444篇 |
国内免费 | 4篇 |
专业分类
6123篇 |
出版年
2023年 | 31篇 |
2022年 | 82篇 |
2021年 | 165篇 |
2020年 | 98篇 |
2019年 | 111篇 |
2018年 | 183篇 |
2017年 | 137篇 |
2016年 | 191篇 |
2015年 | 290篇 |
2014年 | 317篇 |
2013年 | 378篇 |
2012年 | 470篇 |
2011年 | 492篇 |
2010年 | 267篇 |
2009年 | 252篇 |
2008年 | 332篇 |
2007年 | 352篇 |
2006年 | 324篇 |
2005年 | 268篇 |
2004年 | 233篇 |
2003年 | 234篇 |
2002年 | 205篇 |
2001年 | 36篇 |
2000年 | 33篇 |
1999年 | 35篇 |
1998年 | 33篇 |
1997年 | 31篇 |
1996年 | 24篇 |
1995年 | 26篇 |
1994年 | 25篇 |
1993年 | 22篇 |
1992年 | 26篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 22篇 |
1988年 | 10篇 |
1986年 | 14篇 |
1985年 | 21篇 |
1984年 | 24篇 |
1983年 | 23篇 |
1982年 | 20篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 12篇 |
1978年 | 16篇 |
1977年 | 15篇 |
1976年 | 16篇 |
1974年 | 12篇 |
1969年 | 10篇 |
1960年 | 10篇 |
排序方式: 共有6123条查询结果,搜索用时 14 毫秒
971.
972.
Mateus G. Godoy Melissa L.E. Gutarra Fábio M. Maciel Shayany P. Felix Juliana V. Bevilaqua Olga L.T. Machado Denise M.G. Freire 《Enzyme and microbial technology》2009,44(5):317-322
The castor bean (Ricinus communis) represents a potential candidate for biodiesel production. The Petrobras Research Center is developing a biodiesel production process from castor bean seeds, in which an unwanted byproduct named castor bean waste is produced. This extremely alkaline waste is toxic and allergenic and, as such, poses a significant environmental problem. Solid-state fermentation (SSF) of castor bean waste was carried out to achieve ricin detoxification, reduce allergenic potential and stimulate lipase production. The fungus, Penicillium simplicissimum, an excellent lipase producer, was able to grow and produce lipase enzyme. After an optimization process, the maximum lipase activity achieved was 44.8 U/g. Moreover, the fungus P. simplicissimum was able to reduce the ricin content to non-detectable levels in addition to diminishing castor bean waste allergenic potential by approximately 16%. In this way, SSF of castor bean waste by P. simplicissimum may increase the utility of the waste by promoting enzyme production and eliminating the principal toxic element, ricin. 相似文献
973.
Armando Rojas Ivan Schneider Cristian Lindner Ileana Gonzalez Miguel
A. Morales 《Bioscience reports》2022,42(7)
The receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein which actively participates in several chronic inflammation-related diseases. RAGE, in addition to AGEs, has a wide repertoire of ligands, including several damage-associated molecular pattern molecules or alarmins such as HMGB1 and members of the S100 family proteins.Over the last years, a large and compelling body of evidence has revealed the active participation of the RAGE axis in tumor biology based on its active involvement in several crucial mechanisms involved in tumor growth, immune evasion, dissemination, as well as by sculpturing of the tumor microenvironment as a tumor-supportive niche. In the present review, we will detail the consequences of the RAGE axis activation to fuel essential mechanisms to guarantee tumor growth and spreading. 相似文献
974.
Oldfield S Braksator E Rodriguez-Martin I Bailey CP Donaldson LF Henderson G Kelly E 《Journal of neurochemistry》2008,104(4):937-945
The distribution of the mRNA of different C-terminal splice variants of the μ-opioid receptor in rat CNS was assessed by RT-PCR. The mRNA species for MOR1, MOR1A and MOR1B were readily detectable and distributed widely throughout the rat CNS, with levels of MOR1 and MOR1A mRNA being overall greater than for MOR1B. We did not find convincing evidence that significant levels of MOR1C, MOR1C1, MOR1C2 and MOR1D are present in rat CNS. To examine possible differences in the agonist-induced regulation of MOR1, MOR1A and MOR1B, we expressed these constructs in HEK293 cells along with G-protein-coupled inwardly rectifying K+ channel subunits and measured the rate and extent of desensitisation of ( d -Ala2 , N -Me-Phe4 ,glycinol5 )-enkephalin (DAMGO)- and morphine-induced G-protein-coupled inwardly rectifying K+ currents. Morphine-induced desensitisation was rapid for all three splice variants ( t ½ : 1.2–1.7 min) but DAMGO-induced desensitisation was significantly slower for MOR1B ( t ½ 4.2 min). Inhibition of endocytosis by expression of a dynamin-dominant negative mutant increased the rate of DAMGO-induced desensitisation of MOR1B. These data show that some splice variants of μ-opioid receptor are widely expressed in rat CNS but question the existence of others that have been reported in the literature. In addition, whereas the rate of desensitisation of MOR1 and MOR1A is agonist-independent, that for MOR1B is agonist-dependent. 相似文献
975.
Mladenov IV Haralambieva IH Iankov ID Mitov IG 《FEMS immunology and medical microbiology》2002,32(3):249-254
A novel lectin from the root of Arum maculatum was isolated by saline extraction and purified by cold ethanol precipitation and subsequent fractionation on Superose 6 column. The lectin named A. maculatum agglutinin is a non-glycosylated protein with 20-kDa molecular mass agglutinating human ejaculated spermatozoa, but not human erythrocytes. The agglutination was blocked in the presence of N-acetylneuraminic acid indicating that the lectin is sialoglycoprotein specific. Chlamydia pneumoniae strain AR-39 showed considerable potential to grow in murine L-929 fibroblast cells. Pretreatment of the cell monolayers with purified lectin reduced the entry and intracellular replication of C. pneumoniae. These results suggest that the isolated lectin prevents attachment by binding to a C. pneumoniae specific sialoglycoprotein receptor expressed on the surface of L-929 fibroblast cells. 相似文献
976.
Karel Mikulík Anna Jiráňová Jaroslav Weiser Ivan Janda Jana Šťastná Nguyen Quyen 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,740(1):99-107
Slowly cooled cells of Streptomyces aureofaciens contained mainly tight-couple ribosomes. Maximum rate of polyphenylalanine synthesis on ribosomes of S. aureofaciens was observed at 40°C, while cultures grew optimally at 28°C. Ribosomes of S. aureofaciens differed from those of E. coli in the amount of poly(U) required for maximum synthetic activity. The polyphenylalanine-synthesizing activity of E. coli ribosomes was about 3-times higher than that of S. aureofaciens ribosomes. The addition of protein S1 of E. coli or the homologous protein from S. aureofaciens had no stimulatory effect on the translation of poly(U). In order to localize alteration(s) of S. aureofaciens ribosomes in the elongation step of polypeptide synthesis we developed an in vitro system derived from purified elongation factors and ribosomal subunits. The enzymatic binding of Phe-tRNA to ribosomes of S. aureofaciens was significantly lower than the binding to ribosomes of E. coli. This alteration was mainly connected with the function of S. aureofaciens 50 S subunits. These subunits were not deficient in their ability to associate with 30 S subunits or with protein SL5 which is homologous to L7/L12 of E. coli. 相似文献
977.
Monoubiquitination of proliferating cell nuclear antigen (PCNA) enables translesion synthesis (TLS) by specialized DNA polymerases to replicate past damaged DNA. We have studied PCNA modification and chromatin recruitment of TLS polymerases in Xenopus egg extracts and mammalian cells. We show that Xenopus PCNA becomes ubiquitinated and sumoylated after replication stress induced by UV or aphidicolin. Under these conditions the TLS polymerase eta was recruited to chromatin and also became monoubiquitinated. PTIP/Swift is an adaptor protein for the ATM/ATR kinases. Immunodepletion of PTIP/Swift from Xenopus extracts prevented efficient PCNA ubiquitination and polymerase eta recruitment to chromatin during replicative stress. In addition to PCNA ubiquitination, efficient polymerase eta recruitment to chromatin also required ATR kinase activity. We also show that PTIP depletion from mammalian cells by RNAi reduced PCNA ubiquitination in response to DNA damage, and also decreased the recruitment to chromatin of polymerase eta and the recombination protein Rad51. Our results suggest that PTIP/Swift is an important new regulator of DNA damage avoidance in metazoans. 相似文献
978.
Campos IT Silva MM Azzolini SS Souza AF Sampaio CA Fritz H Tanaka AS 《Archives of biochemistry and biophysics》2004,425(1):87-94
A small combinatorial library of LDTI mutants (5.2 x 10(4)) restricted to the P1-P4' positions of the reactive site was displayed on the pCANTAB 5E phagemid, and LDTI fusion phages were produced and selected for potent neutrophil elastase and plasmin inhibitors. Strong fusion phage binders were analyzed by ELISA on enzyme-coated microtiter plates and the positive phages had their DNA sequenced. The LDTI variants: 29E (K8A, I9A, L10F, and K11F) and 19E (K8A, K11Q, and P12Y) for elastase and 2Pl (K11W and P12N), 8Pl (I9V, K11W, and P12E), and 10Pl (I9T, K11L, and P12L) for plasmin were produced with a Saccharomyces cerevisiae expression system. New strong elastase and plasmin inhibitors were 29E and 2Pl, respectively. LDTI-29E was a potent and specific neutrophil elastase inhibitor K(i) =0.5 nM), affecting no other tested enzymes. LDTI-2Pl was the strongest plasmin inhibitor ( K(i) =1.7nM) in the LDTI mutant library. This approach allowed selection of new specific serine proteinase inhibitors for neutrophil elastase and plasmin (a thrombin inhibitor variant was previously described), from a unique template molecule, LDTI, a Kazal type one domain inhibitor, by only 2-4 amino acid replacements. Our data validate this small LDTI combinatorial library as a tool to generate specific serine proteinase inhibitors suitable for drug design and enzyme-inhibitor interaction studies. 相似文献
979.
Rodriguez I 《Hormones and behavior》2004,46(3):219-230
In most mammals, pheromone perception mediates intraspecies interactions related to reproduction, such as mate recognition, intermale aggressive behaviors, or exchanges between females and their offspring. Recent molecular findings, particularly the identification of two large pheromone receptor gene superfamilies, provide today invaluable tools to better understand the way mammals make sense of pheromonal information. 相似文献
980.
Khatibi PA Newmister SA Rayment I McCormick SP Alexander NJ Schmale DG 《Applied and environmental microbiology》2011,77(4):1162-1170
The trichothecene mycotoxin deoxynivalenol (DON) is a common contaminant of small grains, such as wheat and barley, in the United States. New strategies to mitigate the threat of DON need to be developed and implemented. TRI101 and TRI201 are trichothecene 3-O-acetyltransferases that are able to modify DON and reduce its toxicity. Recent work has highlighted differences in the activities of TRI101 from two different species of Fusarium (F. graminearum and F. sporotrichioides), but little is known about the relative activities of TRI101/TRI201 enzymes produced by other species of Fusarium. We cloned TRI101 or TRI201 genes from seven different species of Fusarium and found genetic identity between sequences ranging from 66% to 98%. In vitro feeding studies using transformed yeast showed that all of the TRI101/TRI201 enzymes tested were able to acetylate DON; conversion of DON to 3-acetyl-deoxynivalenol (3ADON) ranged from 50.5% to 100.0%, depending on the Fusarium species from which the gene originated. A time course assay showed that the rate of acetylation varied from species to species, with the gene from F. sporotrichioides having the lowest rate. Steady-state kinetic assays using seven purified enzymes produced catalytic efficiencies for DON acetylation ranging from 6.8 × 10(4) M(-1)·s(-1) to 4.7 × 10(6) M(-1)·s(-1). Thermostability measurements for the seven orthologs ranged from 37.1°C to 43.2°C. Extended sequence analysis of portions of TRI101/TRI201 from 31 species of Fusarium (including known trichothecene producers and nonproducers) suggested that other members of the genus may contain functional TRI101/TRI201 genes, some with the potential to outperform those evaluated in the present study. 相似文献