全文获取类型
收费全文 | 2864篇 |
免费 | 258篇 |
国内免费 | 2篇 |
出版年
2023年 | 17篇 |
2022年 | 25篇 |
2021年 | 92篇 |
2020年 | 43篇 |
2019年 | 72篇 |
2018年 | 92篇 |
2017年 | 85篇 |
2016年 | 82篇 |
2015年 | 150篇 |
2014年 | 174篇 |
2013年 | 198篇 |
2012年 | 266篇 |
2011年 | 260篇 |
2010年 | 156篇 |
2009年 | 121篇 |
2008年 | 195篇 |
2007年 | 201篇 |
2006年 | 171篇 |
2005年 | 159篇 |
2004年 | 159篇 |
2003年 | 136篇 |
2002年 | 130篇 |
2001年 | 13篇 |
2000年 | 15篇 |
1999年 | 14篇 |
1998年 | 17篇 |
1997年 | 19篇 |
1996年 | 10篇 |
1995年 | 4篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1968年 | 2篇 |
1957年 | 1篇 |
1954年 | 1篇 |
1946年 | 1篇 |
排序方式: 共有3124条查询结果,搜索用时 812 毫秒
21.
Shahid N. Khan John D. Persons Michel Guerrero Tatiana V. Ilina Masayuki Oda Rieko Ishima 《Protein science : a publication of the Protein Society》2021,30(3):571
A clinically‐relevant, drug‐resistant mutant of HIV‐1 protease (PR), termed Flap+(I54V) and containing L10I, G48V, I54V and V82A mutations, is known to produce significant changes in the entropy and enthalpy balance of drug‐PR interactions, compared to wild‐type PR. A similar mutant, Flap+(I54A), which evolves from Flap+(I54V) and contains the single change at residue 54 relative to Flap+(I54V), does not. Yet, how Flap+(I54A) behaves in solution is not known. To understand the molecular basis of V54A evolution, we compared nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, isothermal titration calorimetry, and enzymatic assay data from four PR proteins: PR (pWT), Flap+(I54V), Flap+(I54A), and Flap+(I54), a control mutant that contains only L10I, G48V and V82A mutations. Our data consistently show that selection to the smaller side chain at residue 54, not only decreases inhibitor affinity, but also restores the catalytic activity. 相似文献
22.
Goncharov Alexey I. Levina Inna S. Shliapina Viktoriia L. Morozov Ivan A. Rubtsov Petr M. Zavarzin Igor V. Smirnova Olga V. Shchelkunova Tatiana A. 《Biochemistry. Biokhimii?a》2021,86(11):1446-1460
Biochemistry (Moscow) - Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through... 相似文献
23.
Sukhorukov Vladimir S. Mudzhiri Natalia M. Voronkova Anastasia S. Baranich Tatiana I. Glinkina Valeria V. Illarioshkin Sergey N. 《Biochemistry. Biokhimii?a》2021,86(6):667-679
Biochemistry (Moscow) - Alzheimer’s disease is the most common age-related neurodegenerative disease. Understanding of its etiology and pathogenesis is constantly expanding. Thus, the... 相似文献
24.
25.
Mariana C. Pagotti Ana C. B. B. Candido Maria G. Marçal Tatiana M. Vieira Milton Groppo Márcio L. A. Silva Daniele S. Ferreira Viviane R. Esperandim Antônio E. M. Crotti Lizandra G. Magalhães 《化学与生物多样性》2021,18(12):e2100678
Despite the current treatments against Chagas Disease (CD), this vector-borne parasitic disease remains a serious public health concern. In this study, we have explored the in vitro and/or in vivo trypanocidal and cytotoxic activities of the essential oils (EOs) obtained from Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) (DA-EO), Lippia alba (Mill.) N.E. Brown (Verbenaceae) (LA-EO), and Tetradenia riparia (Hochst.) Codd (Lamiaceae) (TR-EO) grown in Brazil Southeast. DA-EO was the most active against the trypomastigote and amastigote forms in vitro; the IC50 values were 8.7 and 12.2 μg mL−1, respectively. The EOs displayed moderate toxicity against LLCMK2 cells, but the DA-EO showed high selectivity index (SI) for trypomastigote (SI=33.2) and amastigote (SI=11.7) forms. Treatment with 20 mg/kg DA-EO, LA-EO, or TR-EO for 20 days by intraperitoneal administration reduced parasitemia by 6.36 %, 4.74 %, and 32.68 % on day 7 and by 12.04 %, 27.96 %, and 65.5 % on day 9. These results indicated that DA-EO, LA-EO, and TR-EO have promising trypanocidal potential in vitro, whereas TR-EO has also potential trypanocidal effects in vivo. 相似文献
26.
John S. Choy Eileen O'Toole Breanna M. Schuster Matthew J. Crisp Tatiana S. Karpova James G. McNally Mark Winey Melissa K. Gardner Munira A. Basrai 《Molecular biology of the cell》2013,24(17):2753-2763
How subunit dosage contributes to the assembly and function of multimeric complexes is an important question with implications in understanding biochemical, evolutionary, and disease mechanisms. Toward identifying pathways that are susceptible to decreased gene dosage, we performed a genome-wide screen for haploinsufficient (HI) genes that guard against genome instability in Saccharomyces cerevisiae. This led to the identification of all three genes (SPC97, SPC98, and TUB4) encoding the evolutionarily conserved γ-tubulin small complex (γ-TuSC), which nucleates microtubule assembly. We found that hemizygous γ-TuSC mutants exhibit higher rates of chromosome loss and increases in anaphase spindle length and elongation velocities. Fluorescence microscopy, fluorescence recovery after photobleaching, electron tomography, and model convolution simulation of spc98/+ mutants revealed improper regulation of interpolar (iMT) and kinetochore (kMT) microtubules in anaphase. The underlying cause is likely due to reduced levels of Tub4, as overexpression of TUB4 suppressed the spindle and chromosome segregation defects in spc98/+ mutants. We propose that γ-TuSC is crucial for balanced assembly between iMTs and kMTs for spindle organization and accurate chromosome segregation. Taken together, the results show how gene dosage studies provide critical insights into the assembly and function of multisubunit complexes that may not be revealed by using traditional studies with haploid gene deletion or conditional alleles. 相似文献
27.
28.
Tatiana Aparecida Voltolin Manolo Penitente Bruna Bueno Mendon?a José Augusto Senhorini Fausto Foresti Fábio Porto-Foresti 《Genetics and molecular biology》2013,36(3):347-352
The family Prochilodontidae is considered a group with well conserved chromosomes characterized by their number, morphology and banding patterns. Thence, our study aimed at accomplishing a cytogenetic analysis with conventional methods (Giemsa staining, silver staining of the nucleolus organizer regions-AgNOR, and C-banding) and fluorescence in situ hybridization (FISH) with 18S and 5S ribosomal DNA probes in five species of the Prochilodus genus (Prochilodus argenteus, Prochilodus brevis, Prochilodus costatus, Prochilodus lineatus and Prochilodus nigricans) collected from different Brazilian hydrographic basins. The results revealed conservatism in chromosome number, morphology, AgNORs 18S and 5S rDNAs location and constitutive heterochromatin distribution patterns. The minor differences observed in this work, such as an Ag-NOR on a P. argenteus chromosome and a distinct C-banding pattern in P. lineatus, are not sufficient to question the conservatism described for this group. Future work using repetitive DNA sequences as probes for FISH will be interesting to further test the cytogenetic conservatism in Prochilodus. 相似文献
29.
Yanjiao Zhou Hongyu Gao Kathie A Mihindukulasuriya Patricio S La Rosa Kristine M Wylie Tatiana Vishnivetskaya Mircea Podar Barb Warner Phillip I Tarr David E Nelson J Dennis Fortenberry Martin J Holland Sarah E Burr William D Shannon Erica Sodergren George M Weinstock 《Genome biology》2013,14(1):R1
Background
Characterizing the biogeography of the microbiome of healthy humans is essential for understanding microbial associated diseases. Previous studies mainly focused on a single body habitat from a limited set of subjects. Here, we analyzed one of the largest microbiome datasets to date and generated a biogeographical map that annotates the biodiversity, spatial relationships, and temporal stability of 22 habitats from 279 healthy humans.Results
We identified 929 genera from more than 24 million 16S rRNA gene sequences of 22 habitats, and we provide a baseline of inter-subject variation for healthy adults. The oral habitat has the most stable microbiota with the highest alpha diversity, while the skin and vaginal microbiota are less stable and show lower alpha diversity. The level of biodiversity in one habitat is independent of the biodiversity of other habitats in the same individual. The abundances of a given genus at a body site in which it dominates do not correlate with the abundances at body sites where it is not dominant. Additionally, we observed the human microbiota exhibit both cosmopolitan and endemic features. Finally, comparing datasets of different projects revealed a project-based clustering pattern, emphasizing the significance of standardization of metagenomic studies.Conclusions
The data presented here extend the definition of the human microbiome by providing a more complete and accurate picture of human microbiome biogeography, addressing questions best answered by a large dataset of subjects and body sites that are deeply sampled by sequencing. 相似文献30.
Thiago Moreno L. Souza Paola C. Resende Natalia Fintelman-Rodrigues Tatiana Schaffer Gregianini Nilo Ikuta Sandra Bianchini Fernandes Ana Luisa Furtado Cury Maria do Carmo Debur Rosa Marilda M. Siqueira 《PloS one》2013,8(11)
Although surveillance efforts that monitor the emergence of drug-resistant strains of influenza are critical, systematic analysis is overlooked in most developing countries. We report on the occurrence of strains of pandemic influenza A(H1N1)pdm09 with resistance and decreased susceptibility to oseltamivir (OST) in Brazil in 2009, 2011 and 2012. We found 7 mutant viruses, 2 with the mutation S247N and other 5 with the mutation H275Y. Most of these viruses were from samples concentrated in the southern region of Brazil. Some of these resistant viruses were detected prior to the initiation of OST treatment, suggesting that community transmission of mutant viruses may exist. Moreover, we show that one of these OST-resistant (H275Y) strains of A(H1N1)pdm09 was discovered in the tri-border region between Brazil, Argentina and Paraguay, highlighting that this strain could also be found in other Latin American countries. Our findings reinforce the importance of enhanced antiviral resistance surveillance in Brazil and in other Latin American countries to confirm or rule out the community transmission of OST-resistant strains of A(H1N1)pdm09. 相似文献