全文获取类型
收费全文 | 2384篇 |
免费 | 184篇 |
国内免费 | 2篇 |
出版年
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 47篇 |
2020年 | 41篇 |
2019年 | 61篇 |
2018年 | 60篇 |
2017年 | 56篇 |
2016年 | 85篇 |
2015年 | 117篇 |
2014年 | 161篇 |
2013年 | 189篇 |
2012年 | 213篇 |
2011年 | 206篇 |
2010年 | 121篇 |
2009年 | 97篇 |
2008年 | 140篇 |
2007年 | 163篇 |
2006年 | 123篇 |
2005年 | 98篇 |
2004年 | 102篇 |
2003年 | 125篇 |
2002年 | 81篇 |
2001年 | 13篇 |
2000年 | 21篇 |
1999年 | 15篇 |
1998年 | 16篇 |
1997年 | 12篇 |
1996年 | 21篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 15篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 12篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1971年 | 3篇 |
1969年 | 3篇 |
1965年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有2570条查询结果,搜索用时 15 毫秒
1.
Léniz A. Portillo M. P. Fernández-Quintela Alfredo Macarulla M. T. Sarasua-Miranda A. del Hoyo M. Díez-López I. 《Journal of physiology and biochemistry》2019,75(3):311-319
Journal of Physiology and Biochemistry - Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later... 相似文献
2.
Fragile X syndrome is a developmental disorder that affects sensory systems. A null mutation of the Fragile X Mental Retardation protein 1 (Fmr1) gene in mice has varied effects on developmental plasticity in different sensory systems, including normal barrel cortical plasticity, altered ocular dominance plasticity and grossly impaired auditory frequency map plasticity. The mutation also has different effects on long-term synaptic plasticity in somatosensory and visual cortical neurons, providing insights on how it may differentially affect the sensory systems. Here we present evidence that long-term potentiation (LTP) is impaired in the developing auditory cortex of the Fmr1 knockout (KO) mice. This impairment of synaptic plasticity is consistent with impaired frequency map plasticity in the Fmr1 KO mouse. Together, these results suggest a potential role of LTP in sensory map plasticity during early sensory development. 相似文献
3.
Amira Alkharusi Elena Lesma Silvia Ancona Eloisa Chiaramonte Thomas Nystr?m Alfredo Gorio Gunnar Norstedt 《PloS one》2016,11(1)
Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects. 相似文献
4.
G. Modiano G. Cermele C. Santolamazza S. Biagioni G. Scarsella L. E. Pacifici G. Toschi 《International Journal of Anthropology》1987,2(1):61-73
392 random patients treated with SCC prior to surgery were assayed for pseudocholinesterase activity and electrophoretic pattern.
The estimate of the percent frequencies of theE
1
a
allele were 1.16±0.38 and of the C5 (+) phenotype 9.7±1.5, both typical of Caucasian populations. By combining the presentE
1
a
gene frequency estimate with that from another sample of the same population (Cermele
et al., 1987) a better estimate with smaller confidence limits was obtained, that is: 1,14±0,27. One subject interpreted asE
1
a
E
1
a
on phenotypic grounds was also found (expected 0,05) in this random sample.
A correlation coefficient of −0.521 was found between E activity and myorelaxation time in the whole sample. High correlation
values (r=−0.55 and r=−0.46) were found forE
1
u
E
1
u
; C5 (−) andE
1
u
E
1
u
; C5 (+) individuals, respectively, showing a strong dependence of the latter variable on the former one even within apparently
homogeneous classes. The use of the product of these two variables as a classification criterion allowed the identification
of a subject with very long myorelaxation time but normal activity. 相似文献
5.
The ratfish,Callorhinchus callorhinchus, a representative of the Holocephali, has a natural serum hemagglutinin (M
r 960 000), composed of heavy (M
r 71000), light (M
r 22 500), and J (M
r 16 000) chains. To approach the mechanisms that generate diversity at this level of evolution, the amino terminal sequence
of the heavy and light chains was determined by automated microsequencing. The chains are unblocked and have modest internal
sequence heterogeneity. The heavy chains show sequence similarity with the terminal region of the heavy chain from the horned
shark,Heterodontus francisci, and other species. In contrast to the heavy chain, the ratfish light chains display low sequence similarity with their shark
kappa counterparts. However, their similarity with the variable region of the chicken lambda light chains is about 75%. 相似文献
6.
Bocco José L. Panzetta Graciela M. Flury Alfredo Patrito Luis C. 《Molecular biology reports》1988,13(1):45-51
Cell-free translation of polyadenylated mRNA from human term placenta in a wheat germ extract, after immunoprecipitation with antibodies directed against purified pregnant serum SP1, yielded a single polypeptide of 31 kDa. Addition of dog pancreatic microsomal vesicles to the translation system resulted in the appearance of two polypeptides, one of them of 46 kDa and the other of 28 kDa. Both polypeptides were protected from limited proteolysis and when the assay was performed with lytic detergent concentrations in addition to proteases, this protection was abolished indicating that the polypeptides were segregated into the microsomal vesicles. The cleavage of a signal peptide of 3 kDa from the 31 kDa primary translation product gives rise to 28 kDa and accounts for the slight increase in electrophoretic mobility. The treatment of the immunoprecipitated products with Endoglycosidase H and -mannosidase, suggested that only the 46 kDa polypeptide is a glycoprotein.From the results obtained we conclude that SP1 is synthesized and processed to a glycoprotein of 46 kDa which would be a protomeric form of the oligomers reported in pregnant serum by other authors.Abbreviations PMSF
phenylmethyl sulfonylfluoride
- TCA
trichloroacetic acid
- DTT
dithiotreitol 相似文献
7.
R Zippel L Morello L Toschi L Alberghina P M Comoglio E Sturani 《Biochimica et biophysica acta》1988,971(3):351-357
The conditions affecting the appearance and disappearance of platelet-derived growth factor (PDGF) receptors from the pool of active cell surface-associated receptors were studied. Receptor molecules were revealed in intact Swiss 3T3 fibroblasts by their ability to bind 125I-labeled PDGF and, due to their property to become phosphorylated in tyrosine following ligand binding, by antibodies to phosphotyrosine. PDGF receptor molecules were found to be quite scarce in exponentially growing fibroblasts as compared to quiescent cells. When growing cells were either shifted to a medium containing plasma or received suramin in the culture medium, cell surface-associated PDGF receptors largely increased. This process required about 12 h. Incubation of quiescent cells in serum, but not in plasma, induced a slow decrement of ligand-activatable receptors. In the presence of PDGF the rate of receptor removal from the cell surface was very rapid and was a function of the PDGF concentration. Quiescent cells deprived of cell-surface receptors by incubation with PDGF reexpressed PDGF receptors in about 14 h. 相似文献
8.
E Sturani L M Vicentini R Zippel L Toschi A Pandiella-Alonso P M Comoglio J Meldolesi 《Biochemical and biophysical research communications》1986,137(1):343-350
Short (1-10 min) pretreatment of intact cells with activators of protein kinase C (e.g. phorbol-12 myristate, 13-acetate, PMA) affects the activity of a variety of surface receptors (for growth factors, hormones and neurotransmitters), with inhibition of transmembrane signal generation. In two types of fibroblasts we demonstrate that the PDGF receptor is unaffected by PMA. Exposure to PMA at concentrations up to 100 nM for 10 min failed to inhibit either one of the agonist-induced, receptor-coupled responses of PDGF: the autophosphorylation of receptor molecules at tyrosine residues, and the hydrolysis of membrane polyphosphoinositides. In contrast, the EGF receptor autophosphorylation (in A 431 cells) and the bombesin-induced phosphoinositide hydrolysis were readily inhibited by PMA. Feed-back inhibition of surface receptors by protein kinase C-mediated phosphorylation is therefore not general, and cannot be the only process responsible for the attenuation of receptor-mediated responses in eukaryotic cells. 相似文献
9.
Alfredo Munoz-Rivas Charles A. Specht Bruce J. Drummond Eunice Froeliger Charles P. Novotny Robert C. Ullrich 《Molecular & general genetics : MGG》1986,205(1):103-106
Summary Protoplasts of aSchizophyllum commune tryptophan auxotroph (trp1), deficient in indole-3-glycerol phosphate synthetase (IGPS), were transformed to trp+ with plasmid DNA containing the SchizophyllumTRP1 sequence. Efficiencies up to 30 transformants per microgram of plasmid DNA were obtained. Southern blots reveal that the
transforming DNA is integrated in chromosomal DNA. The trp+ phenotype of transformants is stable in meiosis and mitosis. Transformants possess IGPS activity comparable to wild-type
cells. 相似文献
10.
Summary A new method of functional morphological analysis is presented. Combining stereophotogrammetry with the finite element technique, a new approach, permits a three-dimensional numerical stress analysis of arbitrarily shaped bodies to be performed. The stereophotogrammetric method which originated for three-dimensional calculations in the study of surfaces in land surveying is well suited for the determination of the nodal co-ordinates required for the finite element method, an engineering technique developed for behavioural analysis of solids and fluids responding to external forces. This approach was tested in a study of the functional morphology of the bill of an African wading bird, the shoebill Balaeniceps rex. A few findings of that study are given here in order to demonstrate the method. Advantages of the finite element method compared with other techniques for stress analysis of anatomical structures are also discussed. The method presents exciting possibilities for predicting displacement and stress responses more accurately and in much greater detail. The scope of this powerful computerized stress analysis technique is greatly enhanced with the introduction of stereophotogrammetry for determining the three-dimensional co-ordinates of complex anatomical structures. With the finite element method, the properties of the bone structure can be modelled as they occur in the life of the animal. This is not possible with physical models. Furthermore, rare specimens can be analysed non-destructively. 相似文献