全文获取类型
收费全文 | 17832篇 |
免费 | 1242篇 |
国内免费 | 2篇 |
出版年
2024年 | 6篇 |
2023年 | 136篇 |
2022年 | 148篇 |
2021年 | 559篇 |
2020年 | 375篇 |
2019年 | 435篇 |
2018年 | 575篇 |
2017年 | 500篇 |
2016年 | 785篇 |
2015年 | 1147篇 |
2014年 | 1208篇 |
2013年 | 1533篇 |
2012年 | 1782篇 |
2011年 | 1565篇 |
2010年 | 984篇 |
2009年 | 826篇 |
2008年 | 1029篇 |
2007年 | 1022篇 |
2006年 | 925篇 |
2005年 | 763篇 |
2004年 | 721篇 |
2003年 | 616篇 |
2002年 | 502篇 |
2001年 | 105篇 |
2000年 | 73篇 |
1999年 | 105篇 |
1998年 | 97篇 |
1997年 | 78篇 |
1996年 | 67篇 |
1995年 | 55篇 |
1994年 | 59篇 |
1993年 | 41篇 |
1992年 | 34篇 |
1991年 | 24篇 |
1990年 | 23篇 |
1989年 | 21篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 15篇 |
1983年 | 15篇 |
1982年 | 5篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1975年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 890 毫秒
101.
Cristiana Iosef Claudio M. Martin Marat Slessarev Carolina Gillio-Meina Gediminas Cepinskas Victor K. M. Han Douglas D. Fraser 《Journal of cellular and molecular medicine》2023,27(1):141-157
Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients. 相似文献
102.
João Ricardo Sato Claudinei Eduardo Biazoli Ana Paula Arantes Bueno Arthur Caye Pedro Mario Pan Marcos Santoro Jessica Honorato-Mauer Giovanni Abrahão Salum Marcelo Queiroz Hoexter Rodrigo Affonseca Bressan Andrea Parolin Jackowski Euripedes Constantino Miguel Sintia Belangero Luis Augusto Rohde 《Genes, Brain & Behavior》2023,22(2):e12838
103.
Diana Villegas-Coronado Jesús Adriana Soto-Guzman Juan Manuel Martínez-Soto Nayelli Guadalupe Teran-Saavedra Ana Maria Guzman-Partida Luz Vazquez-Moreno Ana Gloria Villalba-Villalba Amir Maldonado Irlanda Lagarda-Diaz 《化学与生物多样性》2023,20(7):e202300051
Acute monocytic leukemia is a type of myeloid leukemia that develops in monocytes. The current clinical therapies for leukemia are unsatisfactory due to their side effects and nonspecificity toward target cells. Some lectins display antitumor activity and may specifically recognize cancer cells by binding to carbohydrate structures on their surface. Therefore, this study evaluated the response of the human monocytic leukemia cell lines THP-1 to the Olneya tesota PF2 lectin. The induction of apoptosis and reactive oxygen species production in PF2-treated cells was evaluated by flow cytometry, and the lectin-THP-1 cell interaction and mitochondrial membrane potential were evaluated by confocal fluorescence microscopy. PF2 genotoxicity was evaluated by DNA fragmentation analysis via gel electrophoresis. The results showed that PF2 binds to THP-1 cells, triggers apoptosis and DNA degradation, changes the mitochondrial membrane potential, and increases reactive oxygen species levels in PF2-treated THP-1 cells. These results suggest the potential use of PF2 for developing alternative anticancer treatments with enhanced specificity. 相似文献
104.
Roberto de la Herrán Miguel Hermida Juan Andres Rubiolo Jèssica Gómez-Garrido Fernando Cruz Francisca Robles Rafael Navajas-Pérez Andres Blanco Paula Rodriguez Villamayor Dorinda Torres Pablo Sánchez-Quinteiro Daniel Ramirez Maria Esther Rodríguez Alberto Arias-Pérez Ismael Cross Neil Duncan Teresa Martínez-Peña Ana Riaza Adrian Millán M. Cristina De Rosa Davide Pirolli Marta Gut Carmen Bouza Diego Robledo Laureana Rebordinos Tyler Alioto Carmelo Ruíz-Rejón Paulino Martínez 《Molecular ecology resources》2023,23(4):886-904
Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis. 相似文献
105.
106.
T-box genes are defined by the presence of a conserved sequence, the so-called T-box; this codes for the T-domain, which is involved in DNA-binding and protein dimerisation. Members of this gene family have been found in all metazoans, from diploblasts to humans, and mutations in T-box gene family members in humans have been linked to several congenital disorders. Sequencing of the complete genomes of a range of invertebrate and vertebrate species has allowed the classification of individual T-box genes into five subfamilies: Brachyury, T-brain1, Tbx1, Tbx2 and Tbx6. This review will largely focus on T-box genes identified in organisms whose genomes have been fully sequenced, emphasising how comparative studies of the T-box gene family will help to reveal the roles of these genes during development and in the adult. 相似文献
107.
David L. Cheo Lisiane B. Meira Robert E. Hammer Dennis K. Burns Ana T.B. Doughty Errol C. Friedberg 《Current biology : CB》1996,6(12)
The significance of DNA repair to human health has been well documented by studies on xeroderma pigmentosum (XP) patients, who suffer a dramatically increased risk of cancer in sun-exposed areas of their skin [1] and [2]. This autosomal recessive disorder has been directly associated with a defect in nucleotide excision–repair (NER) [1] and [2]. Like human XP individuals, mice carrying homozygous mutations in XP genes manifest a predisposition to skin carcinogenesis following exposure to ultraviolet (UV) radiation [3], [4] and [5]. Recent studies have suggested that, in addition to roles in apoptosis [6] and cell-cycle checkpoint control [7] in response to DNA damage, p53 protein may modulate NER [8]. Mutations in the p53 gene have been observed in 50% of all human tumors [9] and have been implicated in both the early [10] and late [11] stages of skin cancer. To examine the consequences of a combined deficiency of the XPC and the p53 proteins in mice, we generated double-mutant animals. We document a spectrum of neural tube defects in XPC p53 mutant embryos. Additionally, we show that, following exposure to UV-B radiation, XPC p53 mutant mice have more severe solar keratosis and suffer accelerated skin cancer compared with XPC mutant mice that are wild-type with respect to p53. 相似文献
108.
109.
Ana María Bravo-Angel Heinz-Albert Becker Reinhard Kunze Barbara Hohn Wen-Hui Shen 《Molecular & general genetics : MGG》1995,248(5):527-534
A reverse genetic system for studying excision of the transposable elementDs1 in maize plants has been established previously. In this system, theDs1 element, as part of the genome of maize streak virus (MSV), is introduced into maize plants via agroinfection. In the presence
of theAc element, excision ofDs1 from the MSV genome results in the appearance of viral symptoms on the maize plants. Here, we used this system to study DNA
sequences requiredin cis for excision ofDs1. TheDs1 element contains theAc transposase binding motif AAACGG in only one of its subterminal regions (defined here as the 5′ subterminal region). We showed
that mutation of these motifs abolished completely the excision capacity ofDs1. This is the first direct demonstration that the transposase binding motifs are essential for excision. Mutagenesis with
oligonucleotide insertions in the other (3′) subterminal region resulted in elements with either a reduced or an increased
excision efficiency, indicating that this subterminal region also has an important function. 相似文献
110.
Juan Fernández-Bolaños Rocio Rodríguez Rafael Guillén Ana Jiménez Antonia Heredia 《Physiologia plantarum》1995,93(4):651-658
Enzymatically active cell wall isolaled from olive (Olea europaea) fruit was employed Hi investigate some hydrolytic enzymes bound to the cell wall and the changes in these during ripening. Seven glycosidases. β-glucosidase (EC 3.2.1.21) α-galactosidase (EC 3.2.1.22). β-galactosidase (EC 3.2.1.23). α-arabinosidase (EC 3.2.1.55), α-mannosidase (EC 3.2.1,24). β-xylosidase (EC 3.2.1.37) and β-N-acetylglucosamidase (EC 3.2.1.30). as well as Cx-cellulase (EC 3.2.1.4) and endo-polygalacturonase (EC 3.2.1.15). were identified in the cell wall preparation, at four stages of ripeness (mature green. changing colour, black and black-ripe). Activities of all these cell wall-associated enzymes fionicallv and covalently linked) were determined either by cell wall incubation with artificial substrate or after extraction from the cell wall with buffers of high salt concentration (Cx-cellulase). and were compared to those of forms solubilized from acetone powders with 500 nM citrate buffer (cytoplasmic and/or apoplastic plus ionically hound to cell wall) In general, the activities of low ionic strength buffer-soluble enzymes were found to be much higher than those of the bound enzymes. The bound enzymes are present in the fruit at the green colour stage, whereas the activities of the soluble enzymes only increased from the changing colour stage onwards. The tenacity of binding of enzymes to the wall was investigated by treating the walls with high salt and measuring residual activity. The nature of the ionic and covalent binding and the changes during ripening were also established for wall-hound glycosidase During ripening there was a marked change in the percentages of covalently- and tonically linked activities of β-glucosidase and β-galaclosidase: al the changing colour stages about 75–80% of the bound active in was present in high ionic strength buffer while al the black-ripe stage it was only 15–20. A possible role for these cell wall degradative enzymes in olive softening is discussed. 相似文献