全文获取类型
收费全文 | 27515篇 |
免费 | 1554篇 |
国内免费 | 4177篇 |
专业分类
33246篇 |
出版年
2024年 | 70篇 |
2023年 | 388篇 |
2022年 | 640篇 |
2021年 | 770篇 |
2020年 | 723篇 |
2019年 | 913篇 |
2018年 | 745篇 |
2017年 | 805篇 |
2016年 | 909篇 |
2015年 | 1049篇 |
2014年 | 1313篇 |
2013年 | 1946篇 |
2012年 | 1127篇 |
2011年 | 1300篇 |
2010年 | 1062篇 |
2009年 | 1453篇 |
2008年 | 1525篇 |
2007年 | 1632篇 |
2006年 | 1536篇 |
2005年 | 1484篇 |
2004年 | 1359篇 |
2003年 | 1305篇 |
2002年 | 1082篇 |
2001年 | 858篇 |
2000年 | 712篇 |
1999年 | 672篇 |
1998年 | 690篇 |
1997年 | 564篇 |
1996年 | 527篇 |
1995年 | 538篇 |
1994年 | 509篇 |
1993年 | 406篇 |
1992年 | 384篇 |
1991年 | 291篇 |
1990年 | 243篇 |
1989年 | 230篇 |
1988年 | 212篇 |
1987年 | 165篇 |
1986年 | 122篇 |
1985年 | 163篇 |
1984年 | 191篇 |
1983年 | 122篇 |
1982年 | 125篇 |
1981年 | 79篇 |
1980年 | 60篇 |
1979年 | 62篇 |
1978年 | 47篇 |
1977年 | 26篇 |
1976年 | 40篇 |
1974年 | 26篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
181.
Apparent unbalance between the activities of 6-phosphogluconate and glucose-6-phosphate dehydrogenases in rat liver 总被引:5,自引:0,他引:5
M Sapag-Hagar R Lagunas A Sols 《Biochemical and biophysical research communications》1973,50(1):179-185
The ratio of activities of 6-phosphogluconate dehydrogenase/glucose-6-phosphate dehydrogenase measured in liver extracts of rats in lipogenic nutritional conditions is only 0.2, suggesting an apparent physiological unbalance between the two dehydrogenases of the hexosemonophosphate shunt. This potential unbalance is enhanced by the fact that TPNH is a more powerful competitive inhibitor of 6-phosphogluconate dehydrogenase than of glucose-6-phosphate dehydrogenase. Accordingly, a strong activation of 6-phosphogluconate dehydrogenase would be required for efficient functioning of this pathway, unless there is an alternative outlet for 6-phosphogluconate so far unrecognized in animal tissues. 相似文献
182.
David Dichek Thomas Quertermous 《In vitro cellular & developmental biology. Plant》1989,25(3):289-292
Summary Levels of seven messenger RNA species were compared in human umbilical vein endothelial cells of different lineage and time
in culture. Specifically, cells obtained from the American Type Culture Collection (ATCC) and subcultured were compared to
early passage cells from cultures produced in our laboratory. Messenger RNA for tissue plasminogen activator, plaminogen activator
inhibitor 1, urokinase, and thrombomodulin were expressed at higher levels in the ATCC cells. Thrombospondin, von Willebrand's
Factor, and protein S messenger RNA were expressed at higher levels in the cells that we isolated. In addition, in the ATCC
cells a shift in the proportion of plasminogen activator inhibitor messenger RNA from the 3.4 to the 2.4 kilobase species
was found. We conclude that specific messenger RNA levels can vary considerably between cultured human umbilical vein endothelial
cells. The large variation in mRNA levels which we describe has important implications for experiments involving gene expression
in cultured endothelium. 相似文献
183.
Glutamate dehydrogenase (GDH, E.C. 1.4.1.3) of mustard cotyledons was investigated during the first 4 days of seedling development. The enzyme was found to be composed of seven catalytically active isoforms (each with a molecular mass of 270 kDa) which exhibited a charge heterogeneity when investigated by isoelectric focusing. Antibodies against the purified isoform 7, raised in rabbits, cross-reacted with each of the isoforms in Western blotting experiments. In addition, each of the isoforms was composed of four immunopositive reacting polypeptides with 19, 21, 23 and 25 kDa. During development of the seedlings, a shift in the isoform pattern towards the more acidic forms was found which was more pronounced when the seedlings were supplied with 15 mM NH4Cl. The time course of changes in total GDH level can be correlated with the time course of disappearance of storage proteins. Both parameters are negatively regulated by light possibly via the photoreceptor, phytochrome. There are some indications that GDH in young mustard cotyledons mainly acts in the deaminating direction. 相似文献
184.
Ultrasensitive bioluminescence immunoassays for the determination of peptides and proteins (illustrated with human urinary kallikrein, bradykinin and the determination of human urinary kallikrein antibody titres) have been developed. The usable ranges of the standard curves are from 5 pg to 5000 pg per litre. The relative intra-assay coefficients of variation of the tests were between 2% and 6%, and the inter-assay coefficients of variation between 4% and 12%. 相似文献
185.
Growth factor modulation of melanoma growth stimulatory activity mRNA expression in human malignant melanoma cells correlates with cell growth 总被引:2,自引:0,他引:2
This report demonstrates that the expression of melanoma growth stimulatory activity (MGSA) mRNA can be modulated in a positive fashion in the Hs294T human melanoma cell line by PDGF and MGSA. There is close correlation between MGSA expression and the pattern of cell growth in Hs294T cells. 相似文献
186.
Study of the in vitro bioactivation of albendazole in human liver microsomes and hepatoma cell lines
Sylvie Rolin Hajar Souhaili-El Amri Anne-Marie Batt Michele Levy Denyse Bagrel Gerard Siest 《Cell biology and toxicology》1989,5(1):1-14
The metabolism of albendazole (ABZ), a benzimidazole anthelminthic, was studied in either microsomal preparations of human liver biopsies or cultured human hepatoma cell lines. Metabolites were analyzed by HPLC. Our data show that microsomes from human biopsies and two human cell lines, HepG2 and Hep3B, oxidize the drug to the sulfoxide very efficiently, whereas the third cell line tested, SK-HEP-1, does not. Both cytochrome P-450 dependent monooxygenases and favin-containing monooxygenases appear to be involved in human ABZ metabolism. Using the cell line displaying the highest ABZ-metabolizing activity, HepG2, the cytotoxic and the inducing effects of the parent drug ABZ and of two primary metabolites, the sulfoxide and the sulfone were studied. These three chemicals provoked a rise in mitotic index resulting from cell division blockage at the prophase or at the metaphase (ABZ metabolites) stage, and ABZ was more cytotoxic than its metabolites. With regard to enzyme-inducing effects, our data clearly demonstrate that the sulfoxide and, to a lesser degree, the sulfone are potent inducers of some drug metabolizing enzymes (i.e., cytochrome P-488 dependent monooxygenases and UDP glucuronyltransferase), whereas ABZ fails to increase and even slightly decreases these enzymatic activities. In conclusion, the HepG2 human hepatoma cell line appears to be suitable for the study of many parameters of metabolism and action of ABZ and other structurally related compounds in humans.Abbreviations ABZ
albendazole
- B[a]P
benzo[a]pyrene
- HPLC
high-performance liquid chromatography
- MC
3-methylcholanthrene
- MFO
mixed-function oxidase
- UDPGT
UDP-glucuronyltransferase 相似文献
187.
Short- and Long-Term Alterations of Gene Expression in Limbic Structures by Repeated Electroconvulsive-Induced Seizures 总被引:4,自引:2,他引:2
Vincent Leviel Catherine Fayada Bernard Guibert Michel Chaminade Georges Machek Jacques Mallet Nicole Faucon Biguet† 《Journal of neurochemistry》1990,54(3):899-904
Rats were submitted to a series of 10 daily electroconvulsive shocks (ECS). A first group of animals was killed 1 day after the last seizure and a second group 30 days later. Tyrosine hydroxylase (TH) activity was measured using an in vitro assay in the nucleus caudatus, anterior cortex, amygdala, substantia nigra, ventral tegmental area, and locus ceruleus. The mRNA corresponding to this enzyme (TH-mRNA) was evaluated using a cDNA probe at the cellular level in the ventral tegmental area, substantia nigra, and locus ceruleus. Met-enkephalin (MET)-immunoreactivity and the mRNA coding for the preproenkephalin (PPE-mRNA) were assayed in striatum and the central nucleus of the amygdala. The day after the last ECS an increase of TH activity was observed in the ventral tegmental area, locus ceruleus, and substantia nigra in parallel with a similar increase in the amygdala and striatum; in the anterior cortex TH activity remained unchanged. TH-mRNA was increased in the locus ceruleus, evidencing the presence in this structure of a genomic activation. The amounts of MET and PPE-mRNA were unaffected in the striatum but increased in the amygdala. Thirty days after the last ECS we observed a decrease of TH activity in the amygdala and of TH-mRNA amount in the ventral tegmental area. In the locus ceruleus TH-mRNA remained higher in treated animals than in controls whereas TH activity returned to control levels. These results demonstrate that a series of ECS induces an initial increase of the activity of mesoamygdaloid catecholaminergic neurons followed by a sustained decrease through alterations of TH gene expression which could mediate the clinical effect of the treatment. 相似文献
188.
Joseph G. Major Jr. Melinda E. Wales John E. Houghton Julie A. Maley Jeffrey N. Davidson James R. Wild 《Journal of molecular evolution》1989,28(5):442-450
Summary Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) is the first unique enzyme common to de novo pyrimidine biosynthesis and
is involved in a variety of structural patterns in different organisms. InEscherichia coli, ATCase is a functionally independent, oligomeric enzyme; in hamster, it is part of a trifunctional protein complex, designated
CAD, that includes the preceding and subsequent enzymes of the biosynthetic pathway (carbamoyl phosphate synthetase and dihydroorotase).
The complete complementary DNA (cDNA) nucleotide sequence of the ATCase-encoding portion of the hamster CAD gene is reported
here. A comparison of the deduced amino acid sequences of the hamster andE. coli catalytic peptides revealed an overall 44% amino acid similarity, substantial conservation of predicted secondary structure,
and complete conservation of all the amino acids implicated in the active site of theE. coli enzyme. These observations led to the construction of a functional hybrid ATCase formed by intragenic fusion based on the
known tertiary structure of the bacterial enzyme. In this fusion, the amino terminal half (the “polar domain”) of the fusion
protein was provided by a hamster ATCase cDNA subclone, and the carboxyl terminal portion (the “equatorial domain”) was derived
from a clonedpyrBI operon ofE. coli K-12. The recombinant plasmid bearing the hybrid ATCase was shown to satisfy growth requirements of transformedE. coli pyrB
− cells. The functionality of thisE. coli-hamster hybrid enzyme confirms conservation of essential structure-function relationships between evolutionarily distant
and structurally divergent ATCases. 相似文献
189.
Transformation and expression of a cloned δ-endotoxin gene in bacillus thuringiensis 总被引:6,自引:0,他引:6
Abstract A shuttle vector containing the replication region of a resident plasmid of B. thuringiensis , was used to determine the conditions allowing efficient transformation of B. thuringiensis by electroporation. Using this plasmid a δ-endotoxin gene was cloned and expressed both in Escherichia coli and B. thuringiensis . It was shown that this gene was poorly expressed in the wild type situation whereas after cloning in acrystalliferous strains of B. thuringiensis large amounts of crystal protein were obtained. 相似文献
190.