全文获取类型
收费全文 | 373篇 |
免费 | 24篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 12篇 |
2019年 | 15篇 |
2018年 | 10篇 |
2017年 | 13篇 |
2016年 | 19篇 |
2015年 | 19篇 |
2014年 | 17篇 |
2013年 | 20篇 |
2012年 | 29篇 |
2011年 | 27篇 |
2010年 | 19篇 |
2009年 | 20篇 |
2008年 | 20篇 |
2007年 | 23篇 |
2006年 | 9篇 |
2005年 | 16篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 10篇 |
2001年 | 12篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有398条查询结果,搜索用时 265 毫秒
61.
PD Dr. D. Wieczorek 《Medizinische Genetik》2009,21(2):224-230
Clarification of the cause of mental retardation, which has a prevalence of 2–3%, is a common reason for genetic consultation. On the basis of the cardinal sign of microcephaly, which also has a prevalence of 2–3%, an overview on different conditions with developmental delay/mental retardation is given according to the mode of inheritance. The current version of the Winter–Baraitser Dysmorphology Database lists 558 conditions with the combination of microcephaly and developmental delay/mental retardation. This makes clear that the following overview gives only a limited look at the comprehensive field of clinical genetics/dysmorphology. 相似文献
62.
Renate Radek PD Dr. 《当今生物学》2009,39(4):242-248
Three new, membrane‐bounded organelles were detected in the last decade. Acidocalcisomes which occur in pro‐ and eukaryotes are acidic and store calcium, and further also phosphate, oxygen, magnesium, zink, sodium, potassium, and iron. Furthermore, they are engaged in osmoregulation, pH‐ and Ca2+‐homeostasis. Mitosomes are strongly reduced mitochondria of different parasitic protists, which were previously grouped as primarily mitochondria‐free organisms. Apicoplasts are the strongly reduced plastids of the parasitic apicomplexans (formerly sporozoa). They are a target for the development of new drugs, e.g. against the cause of malaria, Plasmodium. 相似文献
63.
Home ranges of individuals of the gray four-eyed opossum Philander frenatus were studied by capture–mark–recapture (CMR) and radiotelemetry, within a set of eight Atlantic Forest fragments surrounded by a grassland matrix in the state of Rio de Janeiro, southeastern Brazil. Trapping sessions were carried out in all the forest fragments and in the grassland matrix. Adult individuals were fitted with radio-collar transmitters and monitored throughout the night. Locations were obtained by the “homing-in on the animal” method. Home-range sizes of the individuals with five or more captures or locations were estimated through the minimum convex polygon method. Home-range sizes estimated by radiotelemetry ranged from 0.6 to 7.4 ha (n=8), and by CMR ranged from 0.1 to 12.1 ha (n=17); home-range sizes estimated by radiotelemetry did not differ significantly from those based on CMR. However, comparing radiotelemetry with different CMR designs, the former estimates were larger than those based on either CMR using a single grid or CMR using two grids, but not larger than those based on multiple-grid CMR. In specific cases, animals monitored via radiotelemetry for only one or two nights showed larger home ranges than most individuals for which home ranges were estimated by CMR. Two individuals for which home-range sizes were estimated by both techniques showed larger home ranges when data from radiotelemetry were used. These data indicated that CMR can provide results comparable to radiotelemetry when multiple grids, spread across the landscape, are used, although this necessitates an intensive trapping effort. On the other hand, single- and double-grid CMR tend to underestimate home-ranges compared to radiotelemetry. 相似文献
64.
Anna Corcione Elisa Ferretti Maria Bertolotto Franco Fais Lizzia Raffaghello Andrea Gregorio Claudya Tenca Luciano Ottonello Claudio Gambini Glaucia Furtado Sergio Lira Vito Pistoia 《PloS one》2009,4(12)
Background
Fractalkine/CX3CL1, a surface chemokine, binds to CX3CR1 expressed by different lymphocyte subsets. Since CX3CL1 has been detected in the germinal centres of secondary lymphoid tissue, in this study we have investigated CX3CR1 expression and function in human naïve, germinal centre and memory B cells isolated from tonsil or peripheral blood.Methodology/Principal Findings
We demonstrate unambiguously that highly purified human B cells from tonsil and peripheral blood expressed CX3CR1 at mRNA and protein levels as assessed by quantitative PCR, flow cytometry and competition binding assays. In particular, naïve, germinal centre and memory B cells expressed CX3CR1 but only germinal centre B cells were attracted by soluble CX3CL1 in a transwell assay. CX3CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and Src phosphorylation, as assessed by Western blot experiments. CX3CR1+ germinal centre B cells were devoid of centroblasts and enriched for centrocytes that migrated to soluble CX3CL1. ELISA assay showed that soluble CX3CL1 was secreted constitutively by follicular dendritic cells and T follicular helper cells, two cell populations homing in the germinal centre light zone as centrocytes. At variance with that observed in humans, soluble CX3CL1 did not attract spleen B cells from wild type mice. OVA immunized CX3CR1−/− or CX3CL1−/− mice showed significantly decreased specific IgG production compared to wild type mice.Conclusion/Significance
We propose a model whereby human follicular dendritic cells and T follicular helper cells release in the light zone of germinal centre soluble CX3CL1 that attracts centrocytes. The functional implications of these results warrant further investigation. 相似文献65.
66.
Sirtuin proteins form a family of NAD+-dependent protein deacetylases that are considered potential drug targets against parasites. Here, we present the first characterization of a sirtuin orthologue from Leishmania amazonensis, an aetiological agent of American tegumentary leishmaniasis that has been the subject of many studies focused in the development of therapeutic approaches. The protein has high sequence identity with other Kinetoplastid Silent information regulator 2 Related Protein 1 (Sir2RP1) and was named LaSir2RP1. The gene exists as a single copy, encoding a monomeric protein (LaSir2RP1) of approximately 41 kDa that has NAD+-dependent deacetylase activity. LaSir2RP1 was immunodetected in total protein extracts, in cytoplasmic granules, and in the secreted material of both promastigotes and lesion-derived amastigotes. Analysis of both lectin?affinity purified promastigote and amastigote extracts revealed the presence of a major enriched protein of approximately 66 kDa that was recognized by an anti-LaSir2RP1 serum, suggesting that a parasite sirtuin could be glycosylated in vivo. 相似文献
67.
Yan Z Okutsu M Akhtar YN Lira VA 《Journal of applied physiology (Bethesda, Md. : 1985)》2011,110(1):264-274
Skeletal muscle exhibits superb plasticity in response to changes in functional demands. Chronic increases of skeletal muscle contractile activity, such as endurance exercise, lead to a variety of physiological and biochemical adaptations in skeletal muscle, including mitochondrial biogenesis, angiogenesis, and fiber type transformation. These adaptive changes are the basis for the improvement of physical performance and other health benefits. This review focuses on recent findings in genetically engineered animal models designed to elucidate the mechanisms and functions of various signal transduction pathways and gene expression programs in exercise-induced skeletal muscle adaptations. 相似文献
68.
Rosa JC Lira FS Eguchi R Pimentel GD Venâncio DP Cunha CA Oyama LM De Mello MT Seelaender M do Nascimento CM 《Journal of cellular physiology》2011,226(6):1604-1607
Cytokines (IL-6, IL-10, and TNF-α) are increased after exhaustive exercise in the retroperitoneal adipose tissue (RPAT) and mesenteric adipose tissue (MEAT). An exhaustive acute exercise protocol induces inflammation in adipose tissue that lasts 6 h after the exercise has ended. It is well-established that this protocol increases circulating plasma levels of non-esterified fatty acids (NEFAs) and lipopolysaccharides (LPS), compounds that are important in stimulating signaling via toll like receptor-4 (TLR-4) in different type cells. In the present study, we investigated the regulation of TLR-4 and DNA-binding of nuclear factor-κBp65 (NF-κBp65) in different depots of adipose tissue in rats after exhaustive exercise. Rats were killed by decapitation immediately (E0 group, n=6), 2 (E2 group, n=6), and 6 h (E6 group, n=6) after the exhaustive exercise, which consisted of running on a treadmill (approximately 70% V(O2max) ) for 50 min and then running at an elevated rate that increased at 1 m/min, until exhaustion. The control group (C group, n=6) was not subjected to exercise. In RPAT, TLR-4, MYD-88, and IkBα increased in the E2 group after exercise. MYD-88 and TRAF6 remained increased in the E6 group in comparison with the control group. DNA-binding of NF-κBp65 was not altered. In MEAT, TLR-4, MYD-88, TRAF6, and DNA-binding of NF-κBp65 were increased only in the E6 group. In conclusion, we have shown that increases in pro-inflammatory cytokines in adipose tissue pads after exhaustive exercise may be mediated via TLR-4 signaling, leading to increases in NF-κBp65 binding to DNA in MEAT. 相似文献
69.
Günter Müller PD Dr. 《当今生物学》2010,40(1):46-54
Typical civilization diseases, such as type II diabetes, are common, complex in the underlying pathogenic mechanisms, heterogenous in the phenotype and multifactorial due to a wide variety of possible combinations of disease susceptibility or protective genes in different relevant tissues and negative or positive environmental factors. This is in sharp contrast to classical inherited diseases, such as Chorea Huntington, which are often caused by complete loss‐ or gain‐of‐function mutations in a single gene. The causative polymorphisms of susceptibility genes, however, are characterized by relative subtle alterations in the function of the corresponding gene product, which per se do not support the pathogenesis, by high frequency, high expenditure for their identification and rather low predictive value. Consequently, the reliable and early diagnosis of civilization diseases depends on the individual determination of all (or as many as possible) polymorphisms of each susceptibility gene together with the corresponding gene products and the metabolites emerging thereof. 相似文献