全文获取类型
收费全文 | 1214篇 |
免费 | 62篇 |
专业分类
1276篇 |
出版年
2023年 | 3篇 |
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 28篇 |
2017年 | 18篇 |
2016年 | 25篇 |
2015年 | 38篇 |
2014年 | 60篇 |
2013年 | 84篇 |
2012年 | 94篇 |
2011年 | 91篇 |
2010年 | 52篇 |
2009年 | 47篇 |
2008年 | 83篇 |
2007年 | 69篇 |
2006年 | 56篇 |
2005年 | 61篇 |
2004年 | 50篇 |
2003年 | 55篇 |
2002年 | 51篇 |
2001年 | 17篇 |
2000年 | 20篇 |
1999年 | 10篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 7篇 |
1992年 | 17篇 |
1991年 | 5篇 |
1990年 | 16篇 |
1989年 | 18篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 3篇 |
1980年 | 9篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1968年 | 3篇 |
1965年 | 2篇 |
1963年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有1276条查询结果,搜索用时 0 毫秒
1.
2.
Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
3.
Nicholas Cianciotto Terry Serwold-Davis Neal Groman Giulio Ratti Rino Rappuoli 《FEMS microbiology letters》1990,66(1-3):299-301
Chromosomal restriction fragments of Corynebacterium ulcerans and C. diphtheriae, containing an integration site for corynephages of the beta family, show homology on Southern blots. Homologous DNA in also found in the soil isolate C. glutamicum, although this strain is not susceptible to beta-corynephages. Three of these DNA fragments, one for each bacterial strain, and a fragment of gamma-corynephage DNA previously shown to contain the phage integration site, were cloned and sequenced. Alignment of the 3 bacterial sequences shows a very high degree of homology in a stretch of ca 120 nucleotides, whereas the rest of the sequences is generally non-homologous. Within this common bacterial portion, a segment of ca. 96 nucleotides (core sequence) is also highly homologous to the phage sequence. The first half (ca. 50 bp) of the core sequence is identical in all aligned sequences whereas the second half, which is largely occupied by a stem-and-loop structure, contains point mutations peculiar to each clone. The described sequences are likely to be involved in phage integration/excision processes. 相似文献
4.
Summary In the Gasserian ganglion and testis of the rat the endothelium of the small blood vessels has a singular appearance due to the presence of a high number of microvillous processes. These arise from the luminal surface, either individually, or in small groups. The significance of this structure is not known. It is pointed out that these vessels are particularly sensitive to cadmium intoxication.This investigation was performed during a tenure by Dr. Gabbiani of a fellowship of the Medical Research Council of Canada and was supported by the National Institutes of Health (Grant No. 5R01 HE-08794-04) and the Ministère de la Santé du Québec (projet 604-7-635).The authors wish to thank Dr. S. M. Shea for his advice in the measurement of the villi. The technical assistance of Miss Virginia Gilmore and of Mr. Eduardo Garriga is gratefully acknowledged. 相似文献
5.
Rosa Sorrentino Carlo Iannicola Sandro Costanzi Giulio Ratti Carolyn Hurley Roberto Tosi Nobuyuki Tanigaki 《Immunogenetics》1990,32(1):8-12
TR81 is a specificity closely related to or identical with DR3. In Caucasoids two amino acids, Tyr at position 26 and Arg at position 74 of HLA class II DR chains, have been found to be associated with the presence of TR81. Recently, a variant of DRBI *03 identified in American Blacks has been shown to possess Arg at position 74 but Phe at position 26. This codon combination is found to be present in four other cell lines where it still specifies the TR81 determinant. This suggests that the TR81 specificity is uniquely dependent on the presence of Arg at position 74. 相似文献
6.
Massimo Di Giulio 《Journal of molecular evolution》1997,45(6):571-578
A highly complex RNA world, as is sometimes presented in view of the widespread and diversified use of RNA enzymes, would
have encountered many difficulties in passing to a world with catalysis mediated by proteins. These difficulties can be overcome
by postulating a very early relationship between the nucleotide and the amino acid components. In particular, after asserting
that some characteristics expressed by (nucleotide) coenzymes in catalysis are easier to understand if a close and early relationship
between these coenzymes and amino acids is hypothesized, a model is presented for the origin of the enzyme–coenzyme complex.
This model is essentially based on an intermediate formed by a tRNA-like molecule covalently linked to a polypeptide. The
model attributes the majority of the catalytic role in the ribonucleoprotein world to the latter complex and thus it takes
into account the birth of the key intermediate in the origin of protein synthesis—namely, peptidyl-tRNA, which would have
otherwise been extremely difficult to select. The predictions of the model are discussed along with its robustness, using
the data derived from the study of intermediary metabolism and those from molecular biology. Finally, the appearance of the
genetic code in the late phase of the ribonucleopeptide world is discussed.
Received: 13 January 1997 / Accepted: 25 July 1997 相似文献
7.
Dr. Laura Curatolo Christine Chaponnier Maria Benedetta Donati Luciano Morasca Giulio Gabbiani 《Cell and tissue research》1982,223(3):665-673
Summary It is known that human and animal fibroblasts are able to induce the retraction of a fibrin clot. In the present study the correlation between (i) fibrinclot retractile (FCR) activity, (ii) the number of actin stress-lines in mouse fibroblasts during growth in culture, and (iii) the sensitivity of actin stress-lines to a powerful actin-depolymerizing factor (ADF), present in plasma and serum of humans and laboratory animals was investigated. Fibroblasts at early passages (2–4) were tested for these parameters at various intervals after seeding (24, 96, and 168 h). The number of actin stress-lines was progressively higher, while the sensitivity to ADF action was progressively lower in cells cultured from 24 to 168 h; the FCR capacity was significantly decreased at 168 h. These data suggest that cells containing weakly polymerized and/or stabilized actin are more active than those containing highly polymerized and/or stabilized actin in triggering fibroblast contraction. 相似文献
8.
Glutamate as a Putative Transmitter in the Cerebellum: Stimulation by GABA of Glutamic Acid Release from Specific Pools 总被引:8,自引:7,他引:1
The aim of the present paper was to determine whether the release of glutamate from putative "glutamergic" terminals in the cerebellum is influenced by gamma-aminobutyric acid (GABA). In a group of preliminary experiments, we present biochemical evidence in favour of a neurotransmitter role of glutamate in the cerebellum: (1) endogenous glutamate was released from depolarized cerebellar synaptosomal preparations in a Ca2+-dependent away; (2) [14C]glutamate was synthesized from [14C]glutamine in cerebellar synaptosomes, and the newly synthesized [14C]glutamate was released released in a Ca2+-dependent way; (3) the elevation of cyclic GMP elicited by depolarization of cerebellar slices in the presence of Ca2+ was partly reversed by the glutamate antagonist glutamic acid diethyl ester, which probably prevented the interaction of endogenously released glutamate with postsynaptic receptors. GABA and muscimol at low concentrations (2--20 micrometers) potentiated the depolarization-induced release of D-[3H]aspartate (a glutamate analogue which labels the glutamate "reuptake pool") from cerebellar synaptosomes. The effect was concentration dependent and was largely prevented by two GABA antagonists, bicuculline and picrotoxin. The stimulation of D-[3H]aspartate release evoked by muscimol was linearly related to the logarithm of K+ concentration in the depolarizing medium. GABA did not affect the overall release of endogenous glutamate, but potentiated, in a picrotoxin-sensitive manner, the depolarization-evoked release of [14C]glutamate previously synthesized from [14C]glutamine. Since nerve endings are the major site of glutamate synthesis from glutamine, GABA and muscimol appear to exert their stimulatory effect at the level of "glutamergic" nerve terminals, probably after interacting with presynaptic GABA receptors. The possible functional significance of these findings is briefly discussed. 相似文献
9.
10.
Edward J. Leonard Alison Skeel Peter K. Chiang Giulio L. Cantoni 《Biochemical and biophysical research communications》1978,84(1):102-109
An inhibitor of adenosylhomocysteine hydrolase, 3-deazaadenosine, caused profound inhibition of phagocytosis of opsonized erythrocytes by mouse resident peritoneal macrophages . The inhibition was evident at concentrations as low as 2×10?7M, and increased with increasing concentration and time of exposure to the analogue. It was not associated with detachment of the macrophage monolayers or with loss of cell viability. Although the inhibition was not reversible, progression of the functional impairment was interrupted by washing out the analogue. In striking contrast, phagocytic function of human blood monocytes was unaffected by 3-deazaadenosine. 相似文献