全文获取类型
收费全文 | 385篇 |
免费 | 71篇 |
国内免费 | 11篇 |
出版年
2024年 | 3篇 |
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 9篇 |
2020年 | 17篇 |
2019年 | 20篇 |
2018年 | 15篇 |
2017年 | 22篇 |
2016年 | 27篇 |
2015年 | 22篇 |
2014年 | 35篇 |
2013年 | 55篇 |
2012年 | 20篇 |
2011年 | 27篇 |
2010年 | 7篇 |
2009年 | 18篇 |
2008年 | 17篇 |
2007年 | 28篇 |
2006年 | 10篇 |
2005年 | 14篇 |
2004年 | 18篇 |
2003年 | 12篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有467条查询结果,搜索用时 15 毫秒
51.
The cDNA sequence for the human d-bifunctional protein (D-BP: 17β-hydroxysteroid dehydrogenase IV) was investigated in patients with peroxisomal disorders
belonging to the BP complementation group (CG). In three cases, analysis of polymerase chain reaction products generated from
the patients' cDNA indicated the presence of a deletion within the region corresponding to nucleotides 209–537 of the normal
cDNA sequence. Subsequent sequencing revealed that, in two of the patients, 47 base pairs were missing, with the deletion
corresponding to nucleotides 302/3–349/50 of the normal sequence. In the third patient, a smaller deletion of 22 bp (nucleotides
280/1–302/3) was characterized. Only the mutant sequence was detected in each of these cases, consistent with parental consanguinity.
Both deletions cause a frameshift, and would lead to premature termination of the BP. Available family members were also investigated,
and the findings conformed with expectations for an autosomal recessive disorder. In addition to the deletions, a number of
other base changes have been identified in this series of patients. In particular, one patient, whose parents were also consanguineous,
was homozygous for a base change, which results in a nonconservative substitution of serine 177 with a phenylalanine residue.
The functional significance of this amino acid substitution, as well as the other identified changes, is still to be determined.
Nevertheless, our data provide strong support for the hypothesis that defects in the gene for the D-BP are responsible for
the β-oxidation defect in patients belonging to the BP CG. 相似文献
52.
53.
Takashi Uchimura Yoshihiro Komatsu Momo Tanaka Kelly L. McCann Yuji Mishina 《Genesis (New York, N.Y. : 2000)》2009,47(6):374-384
Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During embryogenesis, the compound heterozygous embryos showed several abnormalities, including defects in eye formation, body wall closure defects, and ventricular septal defects (VSD) in the heart. However, the ratio of the compound heterozygous embryos was the same as expected. Caesarean sections at E18.5 revealed that half of the compound heterozygotes died soon after birth, and the majority of the dead individuals exhibited VSD. Survivors were able to grow to adults, but their body weight was significantly lower than control littermates. They demonstrated progressive abnormalities in the heart, eventually showing a branched leaflet in atrioventricular valves. These results suggest that the dosage of both BMP2 and 4 is critical for functional heart formation during embryogenesis and after birth. genesis 47:374–384, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
54.
55.
Hidaka M Su GN Chen JK Mukaisho K Hattori T Yamamoto G 《In vitro cellular & developmental biology. Animal》2007,43(2):49-58
Bone is a complex, highly structured, mechanically active, three-dimensional (3-D) tissue composed of cellular and matrix
elements. We previously published a report on in situ collagen gelation using a rotary 3-D culture system (CG–RC system) for
the construction of large tissue specimens. The objective of the current study was to evaluate the feasibility of bone tissue
engineering using our CG–RC system. Osteoblasts from the calvaria of newborn Wistar rats were cultured in the CG–RC system
for up to 3 wk. The engineered 3-D tissues were implanted into the backs of nude mice and calvarial round bone defects in
Wistar rats. Cell metabolic activity, mineralization, and bone-related proteins were measured in vitro in the engineered 3-D
tissues. Also, the in vivo histological features of the transplanted, engineered 3-D tissues were evaluated in the animal
models. We found that metabolic activity increased in the engineered 3-D tissues during cultivation, and that sufficient mineralization
occurred during the 3 wk in the CG–RC system in vitro. One mo posttransplantation, the transplants to nude mice remained mineralized
and were well invaded by host vasculature. Of particular interest, 2 mo posttransplantation, the transplants into the calvarial
bone defects of rats were replaced by new mature bone. Thus, this study shows that large 3-D osseous tissue could be produced
in vitro and that the engineered 3-D tissue had in vivo osteoinductive potential when transplanted into ectopic locations
and into bone defects. Therefore, this system should be a useful model for bone tissue engineering. 相似文献
56.
57.
The feasibility of using genipin cross-linked type II collagen scaffold with rabbit bone marrow mesenchymal stem cells (RBMSCs)
to repair cartilage defect was herein studied. Induction of RBMSCs into chondrocytic phenotype on type II collagen scaffold
in vitro was conducted using TGF-β 3 containing medium. After 3-weeks of induction, chondrocytic behavior, including marker
genes expression and specific extracellular matrix (ECM) secretion, was observed. In the in vivo evaluation experiment, the
scaffolds containing RBMSCs without prior induction were autologous implanted into the articular cartilage defects made by
subchondral drilling. The repairing ability was evaluated. After 2 months, chondrocyte-like cells with lacuna structure and
corresponding ECM were found in the repaired sites without apparent inflammation. After 24 weeks, we could easily find cartilage
structure the same with normal cartilage in the repair site. In conclusion, it was shown that the scaffolds in combination
of in vivo conditions can induce RBMSCs into chondrocytes in repaired area and would be a possible method for articular cartilage
repair in clinic and cartilage tissue engineering. 相似文献
58.
59.
Weston AD Brown NA Ozolinš TR 《Birth defects research. Part B, Developmental and reproductive toxicology》2011,92(3):206-215
BACKGROUND: The anticonvulsant trimethadione is a potent inducer of ventricular septation defects, both clinically and in rodents. Teratogenicity requires its N‐demethylation to dimethadione, the proximate teratogen. It was previously demonstrated trimethadione only induced membranous ventricular septation defects in rat (Fleeman et al., 2004 ), and our present goal is to determine whether direct administration of dimethadione increases the incidence and severity of septation defects. METHODS: Pregnant Sprague‐Dawley rats were divided into five groups and administered either distilled water (control) or four different regimens of dimethadione. The core treatment was 300 mg/kg dimethadione b.i.d. on gestation day 9, 10 with additional groups given one additional dose of dimethadione 12 hr earlier, 12 hr later or two additional doses 12 hr earlier and later. Caesarian sections occurred on gestation day 21 and fetuses were examined for standard developmental toxicity endpoints. RESULTS: The broadest dosing regimen yielded the highest incidence and the most severe heart and axioskeletal findings with a decrease in mean fetal body weight. The overall incidence of ventricular septation defects was 74%, of which 68% were membranous and 9% muscular. Outflow tract anomalies (17%) were also observed, as were malformations of the axioskeleton (97%), but not of the long bones, and of particular interest was the high incidence of sternoschesis. CONCLUSIONS: Unlike trimethadione, dimethadione induces more serious muscular septation defects that are believed to be more clinically relevant. This, when taken together with the high incidence of total septation anomalies suggests dimethadione is useful for the study of chemically induced ventricular septation defects. Birth Defects Res (Part B) 92:206–215, 2011. © 2011 Wiley‐Liss, Inc. 相似文献