全文获取类型
收费全文 | 588篇 |
免费 | 43篇 |
出版年
2021年 | 7篇 |
2020年 | 10篇 |
2019年 | 7篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 14篇 |
2015年 | 21篇 |
2014年 | 20篇 |
2013年 | 25篇 |
2012年 | 27篇 |
2011年 | 25篇 |
2010年 | 20篇 |
2009年 | 15篇 |
2008年 | 24篇 |
2007年 | 28篇 |
2006年 | 22篇 |
2005年 | 15篇 |
2004年 | 17篇 |
2003年 | 16篇 |
2002年 | 15篇 |
2001年 | 16篇 |
2000年 | 18篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 20篇 |
1996年 | 13篇 |
1995年 | 19篇 |
1994年 | 9篇 |
1993年 | 2篇 |
1992年 | 13篇 |
1991年 | 8篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 11篇 |
1987年 | 13篇 |
1986年 | 14篇 |
1985年 | 8篇 |
1984年 | 5篇 |
1983年 | 10篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1974年 | 6篇 |
1973年 | 7篇 |
1972年 | 4篇 |
1966年 | 2篇 |
排序方式: 共有631条查询结果,搜索用时 5 毫秒
1.
The relationship of hormone-sensitive and hormone-insensitive phosphatidylinositol to phosphatidylinositol 4,5-bisphosphate in the WRK-1 cell 总被引:14,自引:0,他引:14
We have previously characterized two distinct pools of phosphatidylinositol (PI) in the WRK-1 rat mammary tumor cell, one whose metabolism is enhanced in response to vasopressin and another which is insensitive to hormonal manipulation. The purpose of the present study was to examine the relationship between cellular phosphatidylinositol 4,5-bisphosphate (PIP2) and each of the two PI pools. We have found that in WRK-1 cells, vasopressin induces the rapid loss of PIP2 and the accumulation of inositol phosphates. By making use of kinetic differences in 32Pi uptake into the two pools of PI and assessing radioactivity levels in the 1-phosphate of PIP2, we have determined that hormone-sensitive PI is the precursor of approximately 60% of the cellular PIP2; the remainder is synthesized from the hormone-insensitive pool. Additional data indicate that PIP2 derived from hormone-sensitive PI is likewise hormone-sensitive, while that synthesized from hormone-insensitive PI remains stable over a long period of time and is not affected by the presence of vasopressin. 相似文献
2.
James M. Chen Rosalyn Grad Regina Monaco Matthew R. Pincus 《Journal of Protein Chemistry》1996,15(1):11-16
rap-1A, an anti-oncogene-encoded protein, is aras-p21-like protein whose sequence is over 80% homologous to p21 and which interacts with the same intracellular target proteins and is activated by the same mechanisms as p21, e.g., by binding GTP in place of GDP. Both interact with effector proteins in the same region, involving residues 32–47. However, activated rap-1A blocks the mitogenic signal transducing effects of p21. Optimal sequence alignment of p21 and rap-1A shows two insertions of rap-1A atras positions 120 and 138. We have constructed the three-dimensional structure of rap-1A bound to GTP by using the energy-minimized three-dimensional structure ofras-p21 as the basis for the modeling using a stepwise procedure in which identical and homologous amino acid residues in rap-1A are assumed to adopt the same conformation as the corresponding residues in p21. Side-chain conformations for homologous and nonhomologous residues are generated in conformations that are as close as possible to those of the corresponding side chains in p21. The entire structure has been subjected to a nested series of energy minimizations. The final predicted structure has an overall backbone deviation of 0.7 å from that ofras-p21. The effector binding domains from residues 32–47 are identical in both proteins (except for different side chains of different residues at position 45). A major difference occurs in the insertion region at residue 120. This region is in the middle of another effector loop of the p21 protein involving residues 115–126. Differences in sequence and structure in this region may contribute to the differences in cellular functions of these two proteins. 相似文献
3.
F Monaco M Andreoli A La Posta J Roche 《Comparative biochemistry and physiology. B, Comparative biochemistry》1978,60(1):87-91
1. The biosynthesis of 18-19S thyroglobulin has been studied in a larval and adult freshwater lamprey (Lampetra planeri Bl.). 2. In vivo and in vitro experiments have been performed by injecting into the coelomic cavity or by incubating branchial region labeled constituents of Tg of higher vertebrates (125I, [3H]leucine and various [3H]carbohydrates). 3. Larvae (ammocoetes) and adults incorporate all labels into thyroglobulin (18-19S Tg), containing a small proportion of labeled T3 and T4, as identified by paper chromatography, and very minute amounts of stable iodine. 4. In adults, the biosynthesis of 18-19S Tg proceeds much more rapidly and the labels are incorporated in higher percentage than in larvae. 5. The demonstration of the biosynthesis of the specific thyroid protein, 18-19S Tg, in larvae indicates that the biochemical mechanism of hormonogenesis is present in larval endostyle before the morphological differentiation of thyroid cells and follicles occurring during metamorphosis. 6. Some 18-19S Tg is apparently stored in the endostyle. 相似文献
4.
A study of the histology and morphology of the digestive tract of the sea-bream, Sparus aurata 总被引:12,自引:0,他引:12
The anatomy and the histology of the digestive tract of young and adult sea-bream is described from studies using light and scanning electron microscopy. The dentition in the juvenile (25–30 mm long) comprises all canine-like teeth, to which plate teeth and transition elements are added in the adult.
The oesophagus shows a multi-layered mucosa in the upper part, and single-layered regions in the lower part. The multi-layered regions are formed by epithelial cells, mucus-secreting cells and by cells rich with eosinophilic granules.
The Y-shaped stomach, clearly distinguishable, has a single-layered columnar epithelium under which, in the cardiac and fundic portion, gastric glands, comprised of all similar cells, are present. The pyloric region is characterized by four caeca, to the base of which the ductus pancreaticus and the ductus hepaticus discharge.
The pancreas is composed of small masses spread along the upper intestine; in the adult, pancreatic infiltrations can be seen in the liver.
The intestine is short (relative length 0.5–0.6). The intestine epithelium consists of columnar cells intercalated with mucus-secreting cells. A funnel-like valve marks the passage to the intestine terminal region, characterized by a mucosa of cells with an abundance of vacuoles full of eosinophilic granules. 相似文献
The oesophagus shows a multi-layered mucosa in the upper part, and single-layered regions in the lower part. The multi-layered regions are formed by epithelial cells, mucus-secreting cells and by cells rich with eosinophilic granules.
The Y-shaped stomach, clearly distinguishable, has a single-layered columnar epithelium under which, in the cardiac and fundic portion, gastric glands, comprised of all similar cells, are present. The pyloric region is characterized by four caeca, to the base of which the ductus pancreaticus and the ductus hepaticus discharge.
The pancreas is composed of small masses spread along the upper intestine; in the adult, pancreatic infiltrations can be seen in the liver.
The intestine is short (relative length 0.5–0.6). The intestine epithelium consists of columnar cells intercalated with mucus-secreting cells. A funnel-like valve marks the passage to the intestine terminal region, characterized by a mucosa of cells with an abundance of vacuoles full of eosinophilic granules. 相似文献
5.
Summary A DNA deletion in a patient with Becker muscular dystrophy (BMD) has been delineated by restriction endonuclease mapping. The deletion is unusually small, removing six kilobases (kb) of DNA distal to pERT 87-1 (DXS164). This region has previously been shown to contain an exon of a candidate gene which, when defective, causes Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy. Removal of this exon and surrounding DNA is apparently sufficient, in this case, to cause a BMD phenotype. The occurrence of this deletion in DXS164 would appear to confirm that this region is part of the BMD locus. Many DMD patients have deletions in and around this region, adding further evidence for the allelic nature of the two disorders. This fortuitous deletion may identify a functionally important domain of the protein product in terms of the severity of phenotype manifested. 相似文献
6.
Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy 总被引:26,自引:2,他引:24
Anthony P. Monaco Corlee J. Bertelson Chris Colletti-Feener Louis M. Kunkel 《Human genetics》1987,75(3):221-227
Summary Twenty-nine deletion breakpoints were mapped in 220 kb of the DXS164 locus relative to potential exons of the Duchenne and Becker muscular dystrophy gene. Four deletion junction fragments were isolated to acquire outlying Xp21 loci on both the terminal and centromere side of the DXS164 locus. The junction loci were used for chromosome walking, searches for DNA polymorphisms, and mapping against deletion and translocation breakpoints. Forty-four unrelated deletions were analyzed using the junction loci as hybridization probes to map the endpoints between cloned Xp21 loci. DNA polymorphisms from the DXS164 and junction loci were used to follow the segregation of a mutation in a family that represents a recombinant. Both the physical and genetic data point to a very large size for this X-linked muscular dystrophy locus. 相似文献
7.
M A Satta A Castelli M L Maussier A Scoppola V Valenza I Saletnich F Monaco J Roche 《Comptes rendus des séances de la Société de biologie et de ses filiales》1989,183(4):337-341
The effect of naloxone (opioid receptor blocker) on the impairment of growth hormone (GH) release after clonidine (alfa 2-adrenergic agonist) was investigated in 10 volunteer obese subjects. The patients (4 males and 6 females, 16-22 year old) with fat excess (15 +/- 2 kg) estimated by bioelectrical impedance analysis (BIA) were studied repeatedly. The patients, were perfused by a slow saline infusion. 30 min later they received a bolus dose of clonidine (150 micrograms p.o.), followed 30 min later by a bolus dose of naloxone (10 mg i.v.) or a corresponding volume of isotonic sodium cloride (I.S.) for control. No significant changes occurred in blood GH concentration after clonidine administration and naloxone did not induce GH response at clonidine. These results suggest that in obese subjects the impairment of GH release after clonidine is not mediated via receptors sensitivity to naloxone. 相似文献
8.
A 10-megabase physical map of human Xp21, including the Duchenne muscular dystrophy gene 总被引:26,自引:0,他引:26
M Burmeister A P Monaco E F Gillard G J van Ommen N A Affara M A Ferguson-Smith L M Kunkel H Lehrach 《Genomics》1988,2(3):189-202
Using pulsed-field gel electrophoresis and 12 Xp21-derived DNA probes, we have constructed a continuous restriction map spanning more than 4 million base pairs (4 Mbp), including the Duchenne muscular dystrophy gene of more than 2 Mbp. This detailed map is part of a less detailed map spanning 10 Mbp, also spanning the genes for glycerol kinase and congenital adrenal hypoplasia, constructed under electrophoresis conditions which separated DNA fragments in the range 200 to 4000 kbp. DNA from three different tissues was analyzed, and differential methylation was observed. 相似文献
9.
An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus 总被引:78,自引:0,他引:78
Deletions giving rise to Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) occur in the same large gene on the short arm of the human X chromosome. We present a molecular mechanism to explain the clinical difference in severity between DMD and BMD patients who bear partial deletions of the same gene locus. The model is based on the breakpoints of intragenic deletions and their effect on the translation of triplet codons into amino acids of the protein product. Deletions identified in three DMD patients are shown to shift the translational open reading frame (ORF) of triplet codons for amino acids, and each deletion is predicted to result in a truncated, abnormal protein product. Deletions identified in three BMD patients are shown to maintain the translational ORF for amino acids and predict a shorter, lower molecular weight protein. The smaller protein product is presumed to be semifunctional and to result in a milder clinical phenotype. The same ORF mechanism is also applicable to potential 5' and 3' intron splice mutations and their effect on protein production and clinical phenotype. 相似文献
10.
Specific vasopressin binding to WRK-1 rat mammary tumor cells was assessed and compared with vasopressin-induced alterations in phosphatidylinositol metabolism. Scatchard analysis revealed the presence of two binding sites: a saturable, high affinity site with a dissociation constant of 1 X 10(-9) M and an n of 2700 sites per cell, and a nonsaturable, apparent lower affinity site. The higher affinity site appeared to have V1a specificity and to correlate with vasopressin's ability to stimulate phosphatidylinositol turnover in the cells. 相似文献