全文获取类型
收费全文 | 7555篇 |
免费 | 559篇 |
国内免费 | 1篇 |
专业分类
8115篇 |
出版年
2022年 | 37篇 |
2021年 | 56篇 |
2019年 | 62篇 |
2018年 | 77篇 |
2017年 | 58篇 |
2016年 | 84篇 |
2015年 | 149篇 |
2014年 | 197篇 |
2013年 | 529篇 |
2012年 | 295篇 |
2011年 | 293篇 |
2010年 | 179篇 |
2009年 | 183篇 |
2008年 | 290篇 |
2007年 | 346篇 |
2006年 | 304篇 |
2005年 | 312篇 |
2004年 | 332篇 |
2003年 | 279篇 |
2002年 | 316篇 |
2001年 | 286篇 |
2000年 | 327篇 |
1999年 | 282篇 |
1998年 | 95篇 |
1997年 | 80篇 |
1996年 | 55篇 |
1995年 | 84篇 |
1994年 | 74篇 |
1993年 | 65篇 |
1992年 | 179篇 |
1991年 | 227篇 |
1990年 | 173篇 |
1989年 | 167篇 |
1988年 | 192篇 |
1987年 | 164篇 |
1986年 | 143篇 |
1985年 | 137篇 |
1984年 | 107篇 |
1983年 | 83篇 |
1982年 | 67篇 |
1981年 | 75篇 |
1980年 | 55篇 |
1979年 | 77篇 |
1978年 | 70篇 |
1977年 | 48篇 |
1976年 | 42篇 |
1975年 | 45篇 |
1974年 | 41篇 |
1973年 | 46篇 |
1972年 | 39篇 |
排序方式: 共有8115条查询结果,搜索用时 15 毫秒
81.
A two-domain mechanism for group A streptococcal adherence through protein F to the extracellular matrix. 总被引:18,自引:1,他引:17 下载免费PDF全文
V Ozeri A Tovi I Burstein S Natanson-Yaron M G Caparon K M Yamada S K Akiyama I Vlodavsky E Hanski 《The EMBO journal》1996,15(5):989-998
Streptococcus pyogenes binds to the extracellular matrix (ECM) and a variety of host cells and tissues, causing diverse human diseases. Protein F, a S.pyogenes adhesin that binds fibronectin (Fn), contains two binding domains. A repeated domain (RD2) and an additional domain (UR), located immediately N-terminal to RD2. Both domains are required for maximal Fn binding. In this study, we characterize RD2 and UR precisely and compare their functions and binding sites in Fn. The minimal functional unit of RD2 is of 44 amino acids, with contributions from two adjacent RD2 repeats flanked by a novel 'MGGQSES' motif. RD2 binds to the N-terminal fibrin binding domain of Fn. UR contains 49 amino acids, of which six are from the first repeat of RD2. It binds to Fn with higher affinity than RD2, and recognizes a larger fragment that contains fibrin and collagen binding domains. Expression of UR and RD2 independently on the surface-exposed region of unrelated streptococcal protein demonstrates that both mediate adherence of the bacteria to the ECM. We describe here a mechanism of adherence of a pathogen that involves two pairs of sites located on a single adhesin molecule and directed at the same host receptor. 相似文献
82.
Somatic mosaicism of expanded CAG repeats in brains of patients with dentatorubral-pallidoluysian atrophy: cellular population-dependent dynamics of mitotic instability. 总被引:8,自引:1,他引:7 下载免费PDF全文
H. Takano O. Onodera H. Takahashi S. Igarashi M. Yamada M. Oyake T. Ikeuchi R. Koide H. Tanaka K. Iwabuchi S. Tsuji 《American journal of human genetics》1996,58(6):1212-1222
Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease caused by unstable expansion of a CAG repeat in the DRPLA gene. We performed detailed quantitative analysis of the size and the size distribution (range) of the expanded CAG repeats in various regions of the CNS of eight autopsied patients with DRPLA. Expanded alleles (AE) showed considerable variations in size, as well as in range, depending on the region of the CNS, whereas normal alleles did not show such variations, which indicates the occurrence of somatic mosaicism of AE in the CNS. The AE in the cerebellar cortex were consistently smaller by two to five repeat units than those in the cerebellar white matter. Moreover, the AE in the cerebral cortex were smaller by one to four repeat units than those in the cerebral white matter. These results suggest that the smaller AE in the cerebellar and cerebral cortices represent those of neuronal cells. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter showed considerable variation ranging from 9 to 23 repeat units, whereas those in the cerebellar cortex showed little variance and were approximately 7 repeat units. The ranges of the AE in the cerebral cortex, cerebral white matter, and cerebellar white matter were much broader in patients with higher ages at death than they were in patients with lower ages at death, raising the possibility that the range of AE increases with time, as the result of mitotic instability of AE. 相似文献
83.
Yuzo Yamada Minako Matsuda Kozaburo Mikata 《Journal of industrial microbiology & biotechnology》1995,14(6):456-460
Summary Two strains ofEeniella nana were examined for their partial base sequences of 18S and 26S rRNAs. In the partial base sequences of 18S rRNA (prositions 1451 through 1618, 168 bases) the strains ofE. nana have five, five, four and eleven base differences with those ofDekkera bruxellensis (type species).D. anomala (andBrettanomyces anomalus),D. naardenensis andD. custersiana, respectively. In the 26S rRNA partial base sequencings (positions 1611 through 1835, 225 bases and positions 493 through 622, 130 bases) the base differences were 46, 43, 34 and 40 and the percent similarities were 53–54, 51–54, 56–57 and 51–53, respectively. The sequence data obtained are discussed phylogenetically and taxonomically, especially on retention of the generic nameEeniella.This paper is dedicated to Professor Herman Jan Phaff in honor of his 50 years of active research which still continues.Significance of the coenzyme Q system in the classification of yeasts and yeast-like organisms. Part LVIII. For part LVII, see ref. [20]. 相似文献
84.
Kenichiro Nakashima Naotaka Kuroda Shinki Kawaguchi Mitsuhiro Wada Shuzo Akiyama 《Luminescence》1995,10(3):185-191
A sensitive peroxyoxalate chemiluminescent (PO-CL) assay for activities of oxidases (uricase, choline oxidase, cholesterol oxidase and xanthine oxidase) which catalyse a formation of hydrogen peroxide was developed using 4,4′-oxalyl-bis[(trifluoromethylsulphonyl)imino]trimethylene-bis(4-methylmorpholinium)trifluoromethanesulphonate as a chemiluminogenic reagent and 2,4,6,8-tetramorpholinopyrimido[5,4-d]pyrimidine as a fluorophore. The standard curve for hydrogen peroxide was linear over the range 1 × 10?7-1 × 10?4 mol/L. Relative standard deviations for oxidase assays were 5.1–12.7% (n = 10). Detection limits were 1 × 10?3 U/mL for uricase, 5 × 10?4 U/mL for choline oxidase, 5 × 10?3 U/mL for cholesterol oxidase and 5 × 10?4 U/mL xanthine oxidase (sample to blank ratio, 3). 相似文献
85.
Construction of a novel bifunctional biogenic amine receptor by two point mutations of the H2-histamine receptor. 下载免费PDF全文
J. DelValle I. Gantz L. Wang Y. J. Guo G. Munzert T. Tashiro Y. Konda T. Yamada 《Molecular medicine (Cambridge, Mass.)》1995,1(3):280-286
BACKGROUND: H2-histamine receptors mediate a wide range of physiological functions extending from stimulation of gastric acid secretion to induction of human promyelocyte differentiation. We have previously cloned the H2-histamine receptor gene and noted that only three amino acids on the receptor were sufficient to define its specificity and selectivity. Despite only modest overall amino acid homology (34% amino acid identity and 57.5% similarity) between the H2-histamine receptor and the receptor for another monoamine, the beta 2-adrenergic receptor, there is remarkable similarity at their critical ligand binding sites. We hypothesized that, if the specificity and selectivity of both receptors are invested in just three amino acids, it should be possible to convert one of the receptors into one that recognizes the ligand of the other by simple mutations at only one or two sites. MATERIAL AND METHODS: We explored the effect of two single mutations in the fifth transmembrane domain of the H2-histamine receptor, which encompasses the sites that determine H2 selectivity. The canine H2 receptor gene was mutated at Asp186 and Gly187 (Asp186 to Ala186 and Gly187 to Ser187) by oligonuceotide directed mutagenesis. The coding region of both the wild-type and mutated H2 receptors was subcloned into the eukaryotic expression vector, CMVneo, and stably transfected into Hepa cells and L cells. The biological activity of histamine and epinephrine on the expressed receptor was examined by measurement of cellular cAMP production and inositol trisphosphate formation. RESULTS: Hepa cells transfected with the Ala186-Ser187 mutant H2 receptor demonstrated a biphasic rise in cAMP in response to epinephrine with an early phase (ED50 approximately 10(-11) M) that could be inhibited by both propranolol and cimetidine. Epinephrine also induced IP3 generation in the same cells, a biological response that is characteristic of activation of the wild-type H2 but not of the beta-adrenergic receptor. L cells transfected with the Ala186-Ser187 mutant H2 receptor also responded to epinephrine in a cimetidine and propranolol inhibitable manner. CONCLUSIONS: We converted the H2-histamine receptor into a bifunctional one that has characteristics of both histamine and adrenergic receptors by two simple mutations. These results support the hypothesis that ligand specificity is determined by only a few key points on a receptor regardless of the structure of the remainder of the molecule. Our studies have important implications on the design of pharmacological agents targeted for action at physiological receptors. 相似文献
86.
87.
The human gene encoding the mutual signal-transducing subunit (-chain) of granulocyte-macrophage colony-stimulating factor, interleukin-3, and interleukin-5 receptor complexes has been mapped to chromosome 22q13.1 by the fluorescence in situ hybridization method. 相似文献
88.
89.
90.