全文获取类型
收费全文 | 13501篇 |
免费 | 1038篇 |
国内免费 | 844篇 |
专业分类
15383篇 |
出版年
2024年 | 30篇 |
2023年 | 139篇 |
2022年 | 332篇 |
2021年 | 605篇 |
2020年 | 370篇 |
2019年 | 484篇 |
2018年 | 429篇 |
2017年 | 335篇 |
2016年 | 495篇 |
2015年 | 825篇 |
2014年 | 883篇 |
2013年 | 1055篇 |
2012年 | 1224篇 |
2011年 | 1044篇 |
2010年 | 642篇 |
2009年 | 576篇 |
2008年 | 777篇 |
2007年 | 609篇 |
2006年 | 614篇 |
2005年 | 490篇 |
2004年 | 417篇 |
2003年 | 346篇 |
2002年 | 290篇 |
2001年 | 269篇 |
2000年 | 223篇 |
1999年 | 215篇 |
1998年 | 155篇 |
1997年 | 126篇 |
1996年 | 138篇 |
1995年 | 129篇 |
1994年 | 115篇 |
1993年 | 94篇 |
1992年 | 134篇 |
1991年 | 117篇 |
1990年 | 81篇 |
1989年 | 102篇 |
1988年 | 60篇 |
1987年 | 48篇 |
1986年 | 58篇 |
1985年 | 64篇 |
1984年 | 18篇 |
1983年 | 24篇 |
1982年 | 28篇 |
1981年 | 12篇 |
1980年 | 25篇 |
1979年 | 20篇 |
1978年 | 16篇 |
1977年 | 19篇 |
1974年 | 9篇 |
1972年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
911.
Human mu-opioid receptor (HmuOR) with a tag of six consecutive histidines at its carboxyl terminus had been expressed in recombinant baculovirus infected Sf9 insect cells. The maximal binding capacity for the [3H] diprenorphine and [3H]ohmefentanyl (Ohm) were 9.1 +/- 0.7 and 6.52 +/- 0.23 nmol/g protein, respectively. The [3H] diprenorphine or [3H] Ohm binding to the receptor expressed in Sf9 cells was strongly inhibited by mu-selective agonists [D-Ala2, N-methyl-Phe4, glyol5]enkephalin (DAGO), Ohm, and morphine, but neither by delta nor by kappa selective agonist. Na+ (100 mM) and GTP (50 microM) could reduce HmuOR agonists etorphine and Ohm affinity binding to the overexpressed HmuOR. mu-selective agonists DAGO and Ohm effectively stimulated [35S]GTP-gammaS binding (EC50 = 2.7 nM and 6.9 nM) and inhibited forskolin- stimulated cAMP accumulation (IC50 = 0.9 nM and 0.3 nM). The agonist-dependent effects could be blocked by opioid antagonist naloxone or by pretreatment of cells with pertussis toxin (PTX). These results demonstrated that HmuOR overexpressed in Sf9 insect cells functionally coupled to endogenous G(i/o) proteins. 相似文献
912.
d-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) shows cooperative properties for binding coenzymes. The structure of apo-GAPDH from Palinurus versicolor has been solved at 2.0 A resolution by X-ray crystallography. The final model gives a crystallographic R factor of 0.178 in the resolution range 8 to 2 A. The structural comparison with holo-GAPDH from the same species reveals a conformational change induced by coenzyme binding similar to that observed in Bacillus stearothermophilus GAPDH but to a lesser extent. The differences in magnitude during the apo-holo transition between these two enzymes were analyzed with respect to the change of the amino acid composition in the coenzyme binding pocket. In the crystalline state of apo-GAPDH, the overall structures of the subunits are similar to each other; however, significant differences in temperature factors and minor differences in domain rotation upon coenzyme binding were observed for different subunits. These structural features are discussed in relation to the environmental asymmetry of crystallographically independent subunits. 相似文献
913.
The Caenorhabditis briggsae homologue of the Caenorhabditis elegans pag-3 gene was cloned and sequenced. When transformed into a C. elegans pag-3 mutant, the C. briggsae pag-3 gene rescued the pag-3 reverse kinker and lethargic phenotypes. The C. elegans pag-3 gene fused to lacZ was expressed in the same pattern in C. elegans and C. briggsae. Unlike many gene homologues compared between C. elegans and C. briggsae, extensive sequence conservation was found in the non-coding regions upstream of the pag-3 exons, in several of the introns and in the downstream non-coding region. Furthermore, the splice acceptor and splice donor sites were conserved, and the size of the introns and exons was surprisingly similar. The predicted protein sequence of C. briggsae PAG-3 was 85% identical to the protein sequence of C. elegans PAG-3. Because so much of the non-coding region of pag-3 was conserved, the control of pag-3 may be quite complex, involving the binding of many trans-acting factors. These results suggest the evolutionary conservation of the pag-3 gene sequence, its expression and function. 相似文献
914.
915.
Quantitative chromatics analysis for computer imaging of cytologic subtypes of lung cancer stained by Papanicolaou stain 总被引:2,自引:0,他引:2
Shen H Lu YD Zhang YX Piao YJ 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2000,22(3):263-266
OBJECTIVE: To determine the role of quantitative chromatics analysis in the classification of subtypes of lung cancer stained by Papanicolaou stain. STUDY DESIGN: By means of computer image analysis, 60 keratinized squamous carcinoma cells (KSCC), 88 nonkeratinized squamous carcinoma cells (NKSCC) and 150 adenocarcinoma cells (ACC) from lung cancer in sputum smears stained by Papanicolaou stain were analyzed and distinguished based on quantitative colorimetry. The features measured were the content of three primary colors, red (R), green (G) and blue (B) and the coefficients of R, G and B (r, g and b, respectively). Hue, saturation, brightness and gray level were also measured. A stepwise discriminant analysis was carried out. RESULTS: The values of R, G and B and r, g and b, hue and saturation in NKSCC and ACC were significantly different from those of KSCC, and the changes in the three primary colors were more sensitive than those in the gray level. Computer assessment based on three primary color coefficients, hue and saturation yielded accuracy of distinguishing KSCC from NKSCC and KSCC from ACC of 95.2% and 95%, respectively. CONCLUSION: Quantitative analyses of R, G and B and r, g, b and hue and saturation are valuable in distinguishing KSCC from NKSCC and ACC. 相似文献
916.
917.
Protein tyrosine kinase activity has been implicated as part of the signaling mechanism leading to the sperm-induced calcium transient following fertilization. In the present study, we have tested the role of the Fyn kinase in triggering the calcium transient by microinjecting domain-specific fusion proteins encoding regions of Fyn sequence as inhibitors of Fyn function in vivo. A fusion protein encoding the SH2 domain of Fyn caused an increase in the latent period between sperm-egg fusion and the beginning of the calcium transient and reduced the amplitude of the calcium signal. A fusion protein encoding the U + SH3 domains also caused a small increase in the latent period. Microscopic examination revealed that a large percentage of eggs injected with the U+SH3 or SH2 domains became polyspermic as a result of the delayed block to polyspermy. Affinity experiments demonstrated that the U+SH3 and SH2 domains of Fyn were capable of forming a stable complex with phospholipase Cgamma from the sea urchin egg. The results suggest that the Fyn kinase participates in the signaling events leading up to the calcium transient and may directly regulate phospholipase Cgamma activity at fertilization. 相似文献
918.
The inhibitory or antibiotic action of four kinds of the selenomorpholine complex on a strain of Escherichia coli was studied by microcalorimetry. Differences in their capacities to inhibit the metabolism of this bacterium were observed.
The extent and duration of the inhibitory effect on the metabolism as judged from the rate constant, k, and the half-inhibitory concentration, IC50, varied with the different drugs. The rate constant (k) of Escherichia coli (in the log phase) in the presence of the drugs decreased with increasing concentrations of the drugs (C). The relationship of k and C is nearly linear for (1) selenomorpholine and (2) selenomorpholine hydrochloride, but for (3) N,N′-methylene bisselenomorpholine and (4) N-dodecyl selenomorpholine, it is not linear. The experimental results reveal that the sequence of antibiotic activity of selenomorpholines
is (3) and (4)>(1)>(2). 相似文献
919.
Artificial chromosomes: ideal vectors? 总被引:5,自引:0,他引:5
Artificial chromosomes are DNA molecules of predictable structure, which are assembled in vitro from defined constituents that behave with the properties of natural chromosomes. Artificial chromosomes were first assembled in budding yeast and have since been useful in many aspects of yeast genetics. Several attempts have been made at building artificial chromosomes in mammals, although these have been met with limited success. Consequently, mini-chromosomes of defined structure have been developed to address questions regarding mammalian chromosome function and for biotechnological applications. Here we review progress in these areas and consider how it influences plans to build artificial chromosomes in plants and parasites. 相似文献
920.
Werner syndrome (WS) is an autosomal recessive genetic disorder that is manifested by genetic instability and premature onset of age-related diseases, including atherosclerosis and cancer. The gene that is mutated in WS cells (WRN) has been identified recently. Characterizations of the WRN gene product indicate that WRN encodes both a 3'-->5' DNA helicase, belonging to the Escherichiacoli RecQ helicase family, and a 3'-->5' DNA exonuclease. Studies to define the molecular mechanism of WRN-DNA transactions are currently underway in many laboratories. Preliminary results indicate that WRN functions as a key factor in resolving aberrant DNA structures that arise from DNA metabolic processes such as replication, recombination and/or repair, to preserve the genetic integrity in cells. 相似文献