全文获取类型
收费全文 | 14900篇 |
免费 | 937篇 |
国内免费 | 6篇 |
学科分类
生物科学 | 15843篇 |
出版年
2022年 | 85篇 |
2021年 | 144篇 |
2019年 | 103篇 |
2018年 | 144篇 |
2017年 | 130篇 |
2016年 | 231篇 |
2015年 | 345篇 |
2014年 | 388篇 |
2013年 | 873篇 |
2012年 | 692篇 |
2011年 | 689篇 |
2010年 | 380篇 |
2009年 | 419篇 |
2008年 | 657篇 |
2007年 | 648篇 |
2006年 | 656篇 |
2005年 | 669篇 |
2004年 | 692篇 |
2003年 | 665篇 |
2002年 | 625篇 |
2001年 | 552篇 |
2000年 | 549篇 |
1999年 | 464篇 |
1998年 | 196篇 |
1997年 | 193篇 |
1996年 | 165篇 |
1995年 | 127篇 |
1994年 | 142篇 |
1993年 | 147篇 |
1992年 | 351篇 |
1991年 | 319篇 |
1990年 | 322篇 |
1989年 | 297篇 |
1988年 | 247篇 |
1987年 | 243篇 |
1986年 | 221篇 |
1985年 | 194篇 |
1984年 | 156篇 |
1983年 | 147篇 |
1982年 | 137篇 |
1981年 | 120篇 |
1980年 | 97篇 |
1979年 | 120篇 |
1978年 | 101篇 |
1977年 | 87篇 |
1976年 | 95篇 |
1975年 | 75篇 |
1974年 | 90篇 |
1973年 | 95篇 |
1971年 | 70篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Elina Ikonen Jaakko Ignatius Reijo Norio Jorma Palo Leena Peltonen 《Human genetics》1992,89(3):275-280
Summary Huntington disease (HD) is found at exceptionally low frequency in the Finnish population. In this population, linkage disequilibrium was earlier established with markers from the D4S10 and D4S43 loci. We now report a continuation to the restriction fragment length polymorphism haplotype analysis, in combination with a genealogical study of all the Finnish HD families. When the HD pedigrees were systematically traced to the 18th century, only one consanguinity was found, and a high percentage (28%) of the families had foreign ancestors. The majority of the Finnish ancestors were localized to border regions or trade centers of the country following the old postal routes. The observed high risk haplotypes formed with markers from the D4S10 and D4S43 loci were evenly distributed among the HD families in different geographical locations. Consequently, the HD gene(s) has most probably arrived in Finland on several occasions via foreign immigrants during the last few centuries. 相似文献
992.
993.
Point mutations in the upstream region of the α-galactosidase A gene exon 6 in an atypical variant of Fabry disease 总被引:5,自引:0,他引:5
Summary Single point mutations in the upstream region of exon 6 of the -galactosidase A gene were found in two Japanese cases of the cardiac form of Fabry disease; 301ArgGln (902GA) in a case that has already been published and 279GlnGlu (835CG) in a new case. They both expressed markedly low, but significant, amounts of residual activity in COS-1 cells. In contrast, two unrelated cases with classic Fabry disease were found to have different point mutations, which showed a complete loss of enzyme activity in a transient expression assay; 328GlyArg (982GA) in the downstream region of exon 6 in one case and two combined mutations, 66GluGln (196GC)/112ArgCys (334CT), in exon 2 in the other. We conclude, on the basis of the results recorded in this study and those in previous reports, that the pathogenesis of atypical Fabry disease is closely associated with point mutations in the upstream region of exon 6 of the -galactosidase A gene. 相似文献
994.
T Kawano H Kataoka H Nagasawa A Isogai A Suzuki 《Biochemical and biophysical research communications》1992,189(1):221-226
We have identified the cDNAs encoding pheromone biosynthesis activating neuropeptide (PBAN) using PCR technique. The nucleotide sequence showed that the PBAN gene encodes, besides PBAN, diapause hormone and three putative amidated peptides. These four peptides share with PBAN the C-terminal pentapeptide amide which is corresponding to the shortest fragment with pheromonotropic activity. The organization of the PBAN gene is characteristic of several short neuropeptides and has some degree of similarity to that of the gene for the insect neuropeptide FMRFamide. Thus, the PBAN gene products construct a family of structurally related peptides and have various biological functions. 相似文献
995.
Ischemic insult induces neuronal death in the CA1 subfields of the hippocampus which are designated generally as the most vulnerable brain region. Recent studies have shown that acidic and basic fibroblast growth factors are potent trophic factors that support the survival of neurons in many brain regions including the hippocampus. Here we demonstrate that continuous infusion of acidic fibroblast growth factor into the lateral cerebral ventricles beginning 2 days before ischemia prevents the death of the CA1 pyramidal cells in the hippocampus of gerbils. Furthermore, delayed continuous administration of acidic fibroblast growth factor starting 5 min after ischemia is equally protective. The results suggest a possible physiological function for acidic fibroblast growth factor in the normal support of hippocampal CA1 pyramidal cells and neurons in some other brain regions in considering the broad spectrum of responsive neurons. 相似文献
996.
Hayuki Sugimoto Yuichi Nakajima Ayaka Motoyama Erina Katagiri Takeshi Watanabe Kazushi Suzuki 《Biopolymers》2020,111(1):e23339
Chitin-binding protein 21 (CBP21) from Serratia marcescens is a lytic polysaccharide monooxygenase that contains a copper ion as a cofactor. We aimed to elucidate the unfolding mechanism of CBP21 and the effects of Cu2+ on its structural stability at pH 5.0. Thermal unfolding of both apo- and holoCBP21 was reversible. ApoCBP21 unfolded in a simple two-state transition manner. The peak temperature of the DSC curve, tp, for holoCBP21 (74.4°C) was about nine degrees higher than that for apoCBP21 (65.6°C). The value of tp in the presence of excess Cu2+ was around 75°C, indicating that Cu2+ does not dissociate from the protein molecule during unfolding. The unfolding mechanism of holoCBP21 was considered to be as follows: N∙Cu2+ ⇌ U∙Cu2+, where N and U represent the native and unfolded states, respectively. Urea-induced equilibrium unfolding analysis showed that holoCBP21 was stabilized by 35 kJ mol−1 in terms of the Gibbs energy change for unfolding (pH 5.0, 25°C), compared with apoCBP21. The increased stability of holoCBP21 was considered to result from the structural stabilization of the protein-Cu2+ complex itself. 相似文献
997.
Membrane lipid peroxidation results in the production of a variety of aldehydic compounds that play a significant role in aging, drug toxicity and the pathogenesis of a number of human diseases, such as atherosclerosis and cancer. Increased lipid peroxidation and reduced antioxidant status may also contribute to the development of diabetic complications. This study reports that lipid peroxidation end products such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) induce aldehyde reductase (ALR) gene expression. MDA and HNE induce an increase in intracellular peroxide levels; N-Acetyl-L-cysteine (NAC) suppressed MDA- and HNE-induced ALR gene expression. These results indicate that increased levels of intracellular peroxides by MDA and HNE might be involved in the upregulation of ALR. 相似文献
998.
Upon irradiation with 365-nm light, copper(II)-camptothecin significantly produced single- and double-strand breaks of DNA and also induced a marked inactivation of bacteriophage. The nucleotide sequence analysis exhibited considerably random DNA cleavage. The DNA strand scission by the camptothecin-Cu(II)-UV light system, as well as the phage inactivation, was strongly suppressed by bathocuproine and catalase, indicating participation of cuprous species and hydrogen peroxide in the reaction. The present results suggest that (1) Cu(II) ion may play an important role as a cofactor in antitumor action of camptothecin and (2) the combination of copper-camptothecin plus long-wave ultraviolet light is useful against certain cancer treatment as a new photochemotherapy. 相似文献
999.
Site-specific phosphorylation by protein kinase C inhibits assembly-promoting activity of microtubule-associated protein 4 总被引:4,自引:0,他引:4
A Mori H Aizawa T C Saido H Kawasaki K Mizuno H Murofushi K Suzuki H Sakai 《Biochemistry》1991,30(38):9341-9346
We have examined the phosphorylation of bovine microtubule-associated protein 4 (MAP4), formerly named MAP-U, by protein kinase C (PKC). When MAP4 was incubated with PKC, about 1 mol of phosphate was incorporated/mol of MAP4. Phosphorylation of MAP4 caused a remarkable decrease in the ability of the MAP to stimulate microtubule assembly. MAP4 consists of an amino-terminal projection domain and a carboxyl-terminal microtubule-binding domain. The carboxyl-terminal domain is subdivided into a Pro-rich region and an assembly-promoting (AP) sequence region containing four tandem repeats of AP sequence that is conserved in MAP4, MAP2, and tau [Aizawa et al. (1990) J. Biol. Chem. 265, 13849-13855]. In order to identify the site of MAP4 phosphorylated by PKC, a series of expressed MAP4 fragments was prepared and treated with the kinase. A fragment corresponding to the Pro-rich region (P fragment) was phosphorylated, while fragments corresponding to the projection domain and the AP sequence region were not. In addition, chymotryptic digestion of an authentic MAP4 prephosphorylated by PKC revealed that phosphate was incorporated almost exclusively into a 27-kDa fragment containing the carboxyl-terminal half of the Pro-rich region. We investigated the phosphorylation site in MAP4 using the P fragment and found that Ser815 was phosphorylated almost exclusively. We conclude that the phosphorylation of a single Ser residue in the Pro-rich region negatively regulates the assembly-promoting activity of MAP4. 相似文献
1000.
A Yamakawa M Nishizawa K T Fujiwara S Kawai H Kawasaki K Suzuki T Takenawa 《The Journal of biological chemistry》1991,266(26):17580-17583
A complementary DNA (cDNA) clone that encodes phosphatidylinositol 4-kinase (PI 4-kinase) was isolated from a rat brain cDNA library. The deduced amino acid sequence of 697 residues revealed that the protein contains two putative transmembrane sequences and that the N-terminal part of the protein has several sequences representing potential phosphorylation sites for cAMP- and calmodulin-dependent kinase. The C-terminal region is probably a phosphotransferase domain homologous to the kinase region of protein kinase family proteins. Specific antibody against the protein expressed in Escherichia coli successfully immunoprecipitated rat brain PI 4-kinase. The messenger RNA for PI 4-kinase was found predominantly in brain and rat neural cell lines. This PI kinase may play a specific role in neural signal transduction. 相似文献