全文获取类型
收费全文 | 1328篇 |
免费 | 118篇 |
出版年
2023年 | 10篇 |
2022年 | 11篇 |
2021年 | 34篇 |
2020年 | 20篇 |
2019年 | 20篇 |
2018年 | 20篇 |
2017年 | 33篇 |
2016年 | 29篇 |
2015年 | 55篇 |
2014年 | 79篇 |
2013年 | 103篇 |
2012年 | 127篇 |
2011年 | 109篇 |
2010年 | 75篇 |
2009年 | 58篇 |
2008年 | 81篇 |
2007年 | 84篇 |
2006年 | 91篇 |
2005年 | 74篇 |
2004年 | 67篇 |
2003年 | 62篇 |
2002年 | 63篇 |
2001年 | 4篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 18篇 |
1997年 | 10篇 |
1996年 | 14篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 8篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 10篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1964年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有1446条查询结果,搜索用时 15 毫秒
61.
Slowed conduction and thin myelination of peripheral nerves associated with mutant rho Guanine-nucleotide exchange factor 10
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Verhoeven K De Jonghe P Van de Putte T Nelis E Zwijsen A Verpoorten N De Vriendt E Jacobs A Van Gerwen V Francis A Ceuterick C Huylebroeck D Timmerman V 《American journal of human genetics》2003,73(4):926-932
Slowed nerve-conduction velocities (NCVs) are a biological endophenotype in the majority of the hereditary motor and sensory neuropathies (HMSN). Here, we identified a family with autosomal dominant segregation of slowed NCVs without the clinical phenotype of HMSN. Peripheral-nerve biopsy showed predominantly thinly myelinated axons. We identified a locus at 8p23 and a Thr109Ile mutation in ARHGEF10, encoding a guanine-nucleotide exchange factor (GEF) for the Rho family of GTPase proteins (RhoGTPases). Rho GEFs are implicated in neural morphogenesis and connectivity and regulate the activity of small RhoGTPases by catalyzing the exchange of bound GDP by GTP. Expression analysis of ARHGEF10, by use of its mouse orthologue Gef10, showed that it is highly expressed in the peripheral nervous system. Our data support a role for ARHGEF10 in developmental myelination of peripheral nerves. 相似文献
62.
Muriel JM Brannan M Taylor K Johnstone IL Lithgow GJ Tuckwell D 《Developmental biology》2003,260(2):339-351
The cuticle of the nematode Caenorhabditis elegans is a collagenous extracellular matrix which forms the exoskeleton and defines the shape of the worm. We have characterized the C. elegans gene M142.2, and we show that this is a developmentally regulated gene important for cuticle structure. Transgenic worms expressing M142.2 promoter fused to green fluorescent protein showed that M142.2 is expressed in late embryos and L2d predauers, in the hypodermal cells which synthesize the cuticle. The same temporal pattern was seen by RT-PCR using RNA purified from specific developmental stages. A recombinant fragment of M142.2 was expressed in Escherichia coli and used to raise an antiserum. Immunohistochemistry using the antiserum localized M142.2 to the periphery of the alae of L1 and dauers, forming two longitudinal ribbons over the hypodermal cells. Loss-of-function of M142.2 by RNAi resulted in a novel phenotype: dumpy dauers which lacked alae. M142.2 therefore plays a major role in the assembly of the alae and the morphology of the dauer cuticle; because of its similarity to the other cut genes of the cuticle, we have named the gene cut-6. 相似文献
63.
64.
Goel DP Maddaford TG Pierce GN 《American journal of physiology. Heart and circulatory physiology》2002,283(4):H1688-H1694
Myocardial ischemia-reperfusion activates the Na(+)/H(+) exchanger, which induces arrhythmias, cell damage, and eventually cell death. Inhibition of the exchanger reduces cell damage and lowers the incidence of arrhythmias after ischemia-reperfusion. The omega-3 polyunsaturated fatty acids (PUFAs) are also known to be cardioprotective and antiarrhythmic during ischemia-reperfusion challenge. Some of the action of PUFAs may occur via inhibition of the Na(+)/H(+) exchanger. The purpose of our study was to determine the capacity for selected PUFAs to alter cardiac sarcolemmal (SL) Na(+)/H(+) exchange. Cardiac membranes highly enriched in SL vesicles were exposed to 10-100 microM eicosapentanoic acid (EPA) or docosahexanoic acid (DHA). H(+)-dependent (22)Na(+) uptake was inhibited by 30-50% after treatment with > or =50 microM EPA or > or =25 microM DHA. This was a specific effect of these PUFAs, because 50 microM linoleic acid or linolenic acid had no significant effect on Na(+)/H(+) exchange. The SL vesicles did not exhibit an increase in passive Na(+) efflux after PUFA treatment. In conclusion, EPA and DHA can potently inhibit cardiac SL Na(+)/H(+) exchange at physiologically relevant concentrations. This may explain, in part, their known cardioprotective effects and antiarrhythmic actions during ischemia-reperfusion. 相似文献
65.
66.
Barrette-Ng IH Ng KK Mark BL Van Aken D Cherney MM Garen C Kolodenko Y Gorbalenya AE Snijder EJ James MN 《The Journal of biological chemistry》2002,277(42):39960-39966
Arteriviruses are enveloped, positive-stranded RNA viruses and include pathogens of major economic concern to the swine- and horse-breeding industries. The arterivirus replicase gene encodes two large precursor polyproteins that are processed by the viral main proteinase nonstructural protein 4 (nsp4). The three-dimensional structure of the 21-kDa nsp4 from the arterivirus prototype equine arteritis virus has been determined to 2.0 A resolution. Nsp4 adopts the smallest known chymotrypsin-like fold with a canonical catalytic triad of Ser-120, His-39, and Asp-65, as well as a novel alpha/beta C-terminal extension domain that may play a role in mediating protein-protein interactions. In different copies of nsp4 in the asymmetric unit, the oxyanion hole adopts either a collapsed inactive conformation or the standard active conformation, which may be a novel way of regulating proteolytic activity. 相似文献
67.
68.
Gangopadhyay S Jalali F Reda D Peacock J Bristow RG Benchimol S 《Experimental cell research》2002,275(1):122-131
The involvement of p53 as a determinant of chemosensitivity or radiosensitivity is not well understood and is complicated by numerous contradictory reports. Here we have addressed this issue using a series of isogenic clones derived from two neuroblastoma cell lines that express wild-type p53 genes, Nub7 and IMR32. Two different mutant p53 transgenes were used in an attempt to disrupt p53 function in the clones. Our findings indicate that the cellular response is dependent on the genotoxic agent used as well as on the specific p53 transgene used. Cellular radiosensitivity showed no association with apoptosis or with the ability of the cells to arrest in G1 after irradiation. An association was observed, however, between gamma-radiation sensitivity and DNA double-strand break rejoining activity. 相似文献
69.
Hasselbaink DM Roemen TH van der Vusse GJ 《Molecular and cellular biochemistry》2002,239(1-2):101-112
Besides serving as oxidisable substrates, fatty acids (FA) are involved in co- and post-translational modification of proteins (protein acylation). Despite the high rate of fatty acid utilisation in the heart, information on protein acylation in cardiac muscle is scarce. To explore this subject in more detail, we used the H9c2 cell line as an experimental model. After incubation with 3H-palmitate or 3H-myristate, cells were lysed and proteins precipitated, followed by extensive delipidation. The delipidated proteins were subjected to SDS-PAGE and transferred to nitro-cellulose prior to autoradiography. In addition, TLC was used to separate the various lipid classes. The first aspect we addressed was the extent of protein acylation as a function of time, relative to fatty acid incorporation into various lipid classes. Cells were incubated for 30 min, 1 h and 2 h with 100 Ci palmitate (PA, 2.3 nmol) or 125 Ci myristate (MA, 2.5 nmol). Palmitoylation increased from 0.48 ± 0.25 to 1.25 ± 0.56 Ci/mg protein between 30 min to 2 h, while myristoylation increased from 0.25 ± 0.12 to 0.77 ± 0.36 Ci/mg protein. Furthermore, delipidated proteins subjected to autoradiography showed that a set of distinct proteins was labelled with 3H-palmitate. Incorporation into phospholipids (PL) increased from 40–60% of the total amount of radio-labelled PA or MA supplied between 30 min and 2 h. Only the FA pool differed between MA and PA, with a higher FA content present after incubations with MA. Second, we investigated palmitoylation and incorporation into cellular lipids as a function of the amount of PA applied. Palmitoylation showed saturation at high PA concentrations. The percentage incorporation of 3H-PA in the various lipids depended on the amount of PA added: a decline in the PL pool with a concomitant increase in the size of the diacylglycerol pool at high PA concentrations. Third, inhibition of palmitoylation by cerulenin and tunicamycin was investigated. While both were able to inhibit palmitoylation, cerulenin also inhibited the incorporation of PA into various lipid classes, indicating differences in inhibitory action. 相似文献
70.
In the USA, the ocelot (Leopardus pardalis) is a highly endangered felid found only in a few remaining vestiges of native thornshrub brushland in the Lower Rio Grande Valley (LRGV) of extreme southern Texas. From 1987-1998, carcasses of 15 adult ocelots that died of vehicular accidents or natural causes were examined for helminths. All cats had 1-8 (mean = 3) helminth species. All were infected with 1-101 (mean +/- SE = 32 +/- 7) Toxascaris leonina. Other helminths from these ocelots were Alaria marcianae, Brachylaima sp., Mesocestoides lineatus, Taenia rileyi, Oncicola canis, Dirofilaria immitis, Physaloptera rara, Ancylostoma tubaeformae, Cylicospirura chevreuxi, Vogeloides felis, and Metathelazia californica. Additionally, two cats had scarring of the aorta with lesions typical of those caused by Spriocerca lupi, although larval nematodes were not seen. A clinal variation in size of nearly three orders of magnitude was noted in the diplostomatid trematodes in the small intestine of one adult male ocelot. Despite the differences in size, all specimens appeared morphologically identical and were regarded as A. marcianae. Helminth prevalences and abundances, including those of potentially pathogenic species like D. immitis, were low. Although a single heartworm infection may have contributed to the death of one ocelot, helminth infections in general seemed to be of no great consequence to this endangered ocelot population. The helminth fauna of ocelots in the LRGV is reflective of that from wild felids in general; all have been reported previously from the bobcat (Lynx rufus) and mountain lion (Puma concolor) elsewhere in Texas. 相似文献