全文获取类型
收费全文 | 1767篇 |
免费 | 155篇 |
出版年
2023年 | 13篇 |
2022年 | 39篇 |
2021年 | 50篇 |
2020年 | 33篇 |
2019年 | 42篇 |
2018年 | 44篇 |
2017年 | 36篇 |
2016年 | 71篇 |
2015年 | 113篇 |
2014年 | 124篇 |
2013年 | 118篇 |
2012年 | 170篇 |
2011年 | 158篇 |
2010年 | 101篇 |
2009年 | 71篇 |
2008年 | 111篇 |
2007年 | 106篇 |
2006年 | 91篇 |
2005年 | 90篇 |
2004年 | 89篇 |
2003年 | 64篇 |
2002年 | 64篇 |
2001年 | 19篇 |
2000年 | 7篇 |
1999年 | 13篇 |
1998年 | 12篇 |
1997年 | 11篇 |
1996年 | 9篇 |
1995年 | 8篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1966年 | 1篇 |
1955年 | 1篇 |
排序方式: 共有1922条查询结果,搜索用时 15 毫秒
91.
Metazoan NXF1/p15 heterodimers promote export of bulk mRNA through nuclear pore complexes (NPC). NXF1 interacts with the NPC via two distinct structural domains, the UBA-like domain and the NTF2-like scaffold, which results from the heterodimerization of the NTF2-like domain of NXF1 with p15. Both domains feature a single nucleoporin-binding site, and they act synergistically to promote NPC translocation. Whether the NTF2-like scaffold (and thereby p15) contributes only to NXF1/NPC association or is also required for other functions, e.g., to impart directionality to the export process by regulating NXF1/NPC or NXF1/cargo interactions, remains unresolved. Here we show that a minimum of two nucleoporin-binding sites is required for NXF1-mediated export of cellular mRNA. These binding sites can be provided by an NTF2-like scaffold followed by a UBA-like domain (as in the wild-type protein) or by two NTF2-like scaffolds or two UBA-like domains in tandem. In the latter case, the export activity of NXF1 is independent of p15. Thus, as for the UBA-like domain, the function of the NTF2-like scaffold is confined to nucleoporin binding. More importantly, two copies of either of these domains are sufficient to promote directional transport of mRNA cargoes across the NPC. 相似文献
92.
Astrocyte-specific inactivation of the neurofibromatosis 1 gene (NF1) is insufficient for astrocytoma formation 总被引:8,自引:0,他引:8
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Bajenaru ML Zhu Y Hedrick NM Donahoe J Parada LF Gutmann DH 《Molecular and cellular biology》2002,22(14):5100-5113
Individuals with the neurofibromatosis 1 (NF1) inherited tumor syndrome develop low-grade gliomas (astrocytomas) at an increased frequency, suggesting that the NF1 gene is a critical growth regulator for astrocytes. In an effort to determine the contribution of the NF1 gene product, neurofibromin, to astrocyte growth regulation and NF1-associated astrocytoma formation, we generated astrocyte-specific Nf1 conditional knockout mice (Nf1(GFAP)CKO) by using Cre/LoxP technology. Transgenic mice were developed in which Cre recombinase was specifically expressed in astrocytes by embryonic day 14.5. Successive intercrossing with mice bearing a conditional Nf1 allele (Nf1flox) resulted in GFAP-Cre Nf1flox/flox (Nf1(GFAP)CKO) animals. No astrocytoma formation or neurological impairment was observed in Nf1(GFAP)CKO mice after 20 months, but increased numbers of proliferating astrocytes were observed in several brain regions. To determine the consequence of Nf1 inactivation at different developmental times, the growth properties of embryonic day 12.5 and postnatal day 2 Nf1 null astrocytes were analyzed. Nf1 null astrocytes exhibited increased proliferation but lacked tumorigenic properties in vitro and did not form tumors when injected into immunocompromised mouse brains in vivo. Collectively, our results suggest that loss of neurofibromin is not sufficient for astrocytoma formation in mice and that other genetic or environmental factors might influence NF1-associated glioma tumorigenesis. 相似文献
93.
94.
95.
Bartsch M Zorn-Kruppa M Kühl N Genieser HG Schwede F Jastorff B 《Biological chemistry》2003,384(9):1321-1326
In the present study, the cAMP analogs 8-bromo-cAMP (8-Br-cAMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-para-chlorophenylthio-cAMP (8-CPT-cAMP), as well as the corresponding cAMP-acetoxymethyl (AM)-ester-prodrugs were tested in a HPLC study for their membrane permeability, intracellular accumulation and biotransformation. Antiproliferative activities of these compounds were studied in the rat C6 glioma cell line. Chromatographic analysis revealed that the AM-ester analogs of the cyclic nucleotides penetrate quantitatively into rat C6 glioma cells and generate high amounts of their parent cyclic nucleotides intracellularly within 60 min; however, long-term growth inhibition tested in C6 cells is only slightly enhanced with the AM-ester prodrugs of 8-Br-cAMP or DBcAMP. 相似文献
96.
Allosteric enhancement of the affinity of muscarinic receptors for their ligands offers a new way to influence cholinergic neurotransmission. The structure of the allosteric binding domain(s) and the features of agonists, antagonists and modulators which determine the occurrence of either positive or negative cooperativity require clarification. We tested interactions between allosteric modulators alcuronium, strychnine and brucine and eight antagonists at muscarinic receptors expressed in CHO cells. In experiments with unlabeled antagonists, all three modulators enhanced the affinity for 4-diphenylacetoxy-N-dimethylpiperidinium (4-DAMP) at the M2 receptors, and strychnine did so also at the M4 receptors. Positive interactions were also observed between alcuronium and L-hyoscyamine (M2) and scopolamine (M2), between strychnine and butylscopolamine (M4), L-hyoscyamine (M2 and M4) and scopolamine (M4), and between brucine and scopolamine (M2). Positive effects of alcuronium, strychnine and brucine on the affinity of the M2 receptors for 4-DAMP have been confirmed by direct measurements of the binding of [3H]-4-DAMP. A comparison of molecular models of several antagonists which are esters revealed that antagonists in which the distance between the N and the carboxyl C atoms corresponds to five chemical bonds are more likely to display positive cooperativity with alcuronium at the M2 receptors than the antagonists in which the N-carboxyl C distance corresponds to four chemical bonds. 相似文献
97.
98.
Expression of cucumber lipid-body lipoxygenase in transgenic tobacco: lipid-body lipoxygenase is correctly targeted to seed lipid bodies 总被引:2,自引:0,他引:2
A particular isoform of lipoxygenase (LOX, EC 1.13.11.12) localized on lipid bodies has been shown by earlier investigations
to play a role during seed germination in initiating the mobilization of triacylglycerols. On lipid bodies of germinating
cucumber (Cucumis sativus L.) seedlings, the modification of linoleoyl moieties by this LOX precedes the hydrolysis of the ester bonds. We analyzed
the expression and intracellular location of this particular LOX form in leaves and seeds of tobacco (Nicotiana tabacum L.) transformed with one construct coding for cucumber lipid-body LOX and one construct coding for cucumber LOX fused with
a hemagglutinin epitope. In both tissues, the amount of lipid-body LOX was clearly detectable. Biochemical analysis revealed
that in mature seeds the foreign LOX was targeted to lipid bodies, and the preferred location of the LOX on lipid bodies was
verified by immunofluorescence microscopy. Cells of the endosperm and of the embryo exhibited fluorescence based on the immunodecoration
of LOX protein whereas very weak fluorescent label was visible in seeds of untransformed control plants. Further cytochemical
analysis of transformed plants showed that the LOX protein accumulated in the cytoplasm when green leaves lacking lipid bodies
were analyzed. Increased LOX activity was shown in young leaves of transformed plants by an increase in the amounts of endogenous
(2E)-hexenal and jasmonic acid.
Received: 9 August 1999 / Accepted: 28 September 1999 相似文献
99.
Zsofia Herbert Sandra Rauser Leslie Williams Neval Kapan Michaela Güntner Axel Walch George Boyan 《Journal of morphology》2010,271(12):1509-1526
The central complex is a major integrative region within the insect brain with demonstrated roles in spatial orientation, the regulation of locomotor behavior, and sound production. In the hemimetabolous grasshopper, the central complex comprises the protocerebral bridge, central body (CB), ellipsoid body, noduli, and accessory lobes, and this modular organization develops entirely during embryogenesis. From a biochemical perspective, a range of neuroactive substances has been demonstrated in these modules of the adult central complex, but little is known about their developmental expression. In this study, we use matrix‐assisted laser desorption/ionization‐imaging mass spectrometry on single brain slices to confirm the presence of several peptide families (tachykinin, allatostatin, periviscerokinin/pyrokinin, FLRFamide, and neuropeptide F) in the adult central complex and then use immunohistochemistry and histology to examine their developmental expression, together with that of the indolamin serotonin, and the endogenous messenger nitric oxide (NO; via its synthesizing enzyme). We find that each neuromodulator is expressed according to a unique, stereotypic, pattern within the various modules making up the central complex. Neuropeptides such as tachykinin (55%) and allatostatin (65%), and the NO‐synthesizing enzyme diaphorase (70%), are expressed earlier during embryonic development than the biogenic amine serotonin (80%), whereas periviscerokinin‐like peptides and FLRFamide‐like peptides begin to be expressed only postembryonically. Within the CB, these neuroactive substances are present in tangential projection neurons before they appear in columnar neurons. There is also no colocalization of serotonin‐positive and peptide‐positive projections up to the third larval instar during development, consistent with the clear dorsoventral layering of the neuropil we observe. Our results provide the first neurochemical fingerprint of the developing central complex in an hemimetabolous insect. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
100.
Timing of reproduction in a Darwin''s finch: temporal opportunism under spatial constraints 总被引:1,自引:0,他引:1
We investigated whether predation by the minor grison ( Galictis cuja , a small mustelid) played a key role in limiting a wild cavy population ( Cavia magna ), ultimately leading to its local extinction. Radio-telemetry and capture-mark-recapture techniques were used to estimate grison predation rates (kill rates), time-specific probabilities of apparent mortality (population loss rate), overall mortality and grison predation for the cavy population. Additionally, we present data on alternative prey species, grison diet and reproduction to show potential proximate mechanisms of grison predation on wild cavies. The predictions specified were mostly confirmed: (1) grison predation was responsible for almost 80% of the cavies killed by known predators; (2) grison predation probabilities paralleled those of overall mortality of cavies over time; and (3) also those of the apparent mortality of the population. Thus, the population dynamics and the local extinction of the cavy population were not due to emigration processes. (4) Grison predation rates were not density-dependent, but showed pronounced peaks during the austral summer. The grison mainly preyed on small mammals: two water-rat species and the wild cavies. When the availability of alternative prey decreased in summer, the grison appeared to specialise on cavies. The onset of grison reproduction was somewhat delayed in relation to the onset of cavy reproduction. The lack of alternative prey coincided with high grison food demands due to reproduction, leading to a very high predation pressure ultimately resulting in the local extinction of the cavy population. We conclude that grison predation was indeed the main factor driving changes of the cavy population studied and speculate why caviomorph rodents might be especially susceptible to local extinction processes. 相似文献