全文获取类型
收费全文 | 6831篇 |
免费 | 481篇 |
国内免费 | 1篇 |
专业分类
7313篇 |
出版年
2024年 | 6篇 |
2023年 | 40篇 |
2022年 | 115篇 |
2021年 | 181篇 |
2020年 | 138篇 |
2019年 | 163篇 |
2018年 | 209篇 |
2017年 | 160篇 |
2016年 | 281篇 |
2015年 | 449篇 |
2014年 | 437篇 |
2013年 | 571篇 |
2012年 | 650篇 |
2011年 | 623篇 |
2010年 | 340篇 |
2009年 | 310篇 |
2008年 | 389篇 |
2007年 | 369篇 |
2006年 | 333篇 |
2005年 | 302篇 |
2004年 | 257篇 |
2003年 | 212篇 |
2002年 | 235篇 |
2001年 | 41篇 |
2000年 | 28篇 |
1999年 | 40篇 |
1998年 | 53篇 |
1997年 | 28篇 |
1996年 | 34篇 |
1995年 | 23篇 |
1994年 | 28篇 |
1993年 | 23篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 13篇 |
1985年 | 9篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 5篇 |
1974年 | 6篇 |
1973年 | 14篇 |
排序方式: 共有7313条查询结果,搜索用时 0 毫秒
11.
NAD-linked lactate, malate, glycerophosphate, alcohol and nonspecific dehydrogenases, aspartate aminotransferases, and soluble esterases from extracts of tissues of individuals from a wild population of Calomys musculinus (Rodentia, Cricetidae) have been analyzed by means of starch gel electrophoresis and specific staining. Allelic frequencies and heterozygosity have been determined. Mendelian inheritance of some of the variants detected was confirmed by breeding experiments. Ten out of fifteen (66.6%) of the genetic loci investigated presented polymorphism. Mean heterozygosity per locus was very high (H=0.2014, se 0.046).This work has been supported, in part, by grants from the Secretaria de Ciencia y Tecnología de la Nación (National Program for Endemic Diseases) and from the Fundación Emilio Ocampo. C. N. G. is a Fellow and A. B. a Career Investigator of the Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina. 相似文献
12.
Anna Junkiert-Czarnecka Maria Pilarska-Deltow Aneta Bk Marta Heise Anna Latos-Bieleska Jacek Zaremba Alicja Bartoszewska-Kubiak Olga Haus 《Current issues in molecular biology》2022,44(4):1472
Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet. 相似文献
13.
14.
Miguel López-Estepa Ana Ardá Martin Savko Adam Round William E. Shepard Marta Bruix Miquel Coll Francisco J. Fernández Jesús Jiménez-Barbero M. Cristina Vega 《PloS one》2015,10(4)
Cyclic N6-threonylcarbamoyladenosine (‘cyclic t6A’, ct6A) is a non-thiolated hypermodification found in transfer RNAs (tRNAs) in bacteria, protists, fungi and plants. In bacteria and yeast cells ct6A has been shown to enhance translation fidelity and efficiency of ANN codons by improving the faithful discrimination of aminoacylated tRNAs by the ribosome. To further the understanding of ct6A biology we have determined the high-resolution crystal structures of CsdL/TcdA in complex with AMP and ATP, an E1-like activating enzyme from Escherichia coli, which catalyzes the ATP-dependent dehydration of t6A to form ct6A. CsdL/TcdA is a dimer whose structural integrity and dimer interface depend critically on strongly bound K+ and Na+ cations. By using biochemical assays and small-angle X-ray scattering we show that CsdL/TcdA can associate with tRNA with a 1:1 stoichiometry and with the proper position and orientation for the cyclization of t6A. Furthermore, we show by nuclear magnetic resonance that CsdL/TcdA engages in transient interactions with CsdA and CsdE, which, in the latter case, involve catalytically important residues. These short-lived interactions may underpin the precise channeling of sulfur atoms from cysteine to CsdL/TcdA as previously characterized. In summary, the combination of structural, biophysical and biochemical methods applied to CsdL/TcdA has afforded a more thorough understanding of how the structure of this E1-like enzyme has been fine tuned to accomplish ct6A synthesis on tRNAs while providing support for the notion that CsdA and CsdE are able to functionally interact with CsdL/TcdA. 相似文献
15.
16.
17.
Szoszkiewicz Krzysztof Jusik Szymon Lewin Iga Czerniawska-Kusza Izabela Kupiec Jerzy Mirosław Szostak Marta 《Hydrobiologia》2018,808(1):327-342
Hydrobiologia - The aim of the study was to compare the patterns of development of macrophytes and macroinvertebrates in different types of reference mountain rivers. The study is based on... 相似文献
18.
Pere Tubert Douglas V. Laurents Marc Ribó Marta Bruix Maria Vilanova Antoni Benito 《Biophysical journal》2011,(2):459-467
The structural determinants that are responsible for the formation of higher order associations of folded proteins remain unknown. We have investigated the role on the dimerization process of different residues of a domain-swapped dimer human pancreatic ribonuclease variant. This variant is a good model to study the dimerization and swapping processes because dimer and monomer forms interconvert, are easily isolated, and only one dimeric species is produced. Thus, simple models for the swapping process can be proposed. The dimerization (dissociation constant) and swapping propensity have been studied using different variants with changes in residues that belong to different putative molecular determinants of dimerization. Using NMR spectroscopy, we show that these mutations do not substantially alter the overall conformation and flexibility, but affect the residue level stability. Overall, the most critical residues for the swapping process are those of one subunit that interact with the hinge loop of another one-subunit residue, stabilizing it in a conformation that favors the interchange. Tyr25, Gln101, and Pro19, with Asn17, Ser21, and Ser23, are found to be the most significant; notably, Glu103 and Arg104, which were postulated to form salt bridges that would stabilize the dimer, are not critical for dimerization. 相似文献
19.
Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels 总被引:13,自引:0,他引:13
Fischer C Jonckx B Mazzone M Zacchigna S Loges S Pattarini L Chorianopoulos E Liesenborghs L Koch M De Mol M Autiero M Wyns S Plaisance S Moons L van Rooijen N Giacca M Stassen JM Dewerchin M Collen D Carmeliet P 《Cell》2007,131(3):463-475
Novel antiangiogenic strategies with complementary mechanisms are needed to maximize efficacy and minimize resistance to current angiogenesis inhibitors. We explored the therapeutic potential and mechanisms of alphaPlGF, an antibody against placental growth factor (PlGF), a VEGF homolog, which regulates the angiogenic switch in disease, but not in health. alphaPlGF inhibited growth and metastasis of various tumors, including those resistant to VEGF(R) inhibitors (VEGF(R)Is), and enhanced the efficacy of chemotherapy and VEGF(R)Is. alphaPlGF inhibited angiogenesis, lymphangiogenesis, and tumor cell motility. Distinct from VEGF(R)Is, alphaPlGF prevented infiltration of angiogenic macrophages and severe tumor hypoxia, and thus, did not switch on the angiogenic rescue program responsible for resistance to VEGF(R)Is. Moreover, it did not cause or enhance VEGF(R)I-related side effects. The efficacy and safety of alphaPlGF, its pleiotropic and complementary mechanism to VEGF(R)Is, and the negligible induction of an angiogenic rescue program suggest that alphaPlGF may constitute a novel approach for cancer treatment. 相似文献