全文获取类型
收费全文 | 6853篇 |
免费 | 484篇 |
国内免费 | 1篇 |
专业分类
7338篇 |
出版年
2024年 | 6篇 |
2023年 | 40篇 |
2022年 | 115篇 |
2021年 | 182篇 |
2020年 | 138篇 |
2019年 | 163篇 |
2018年 | 210篇 |
2017年 | 160篇 |
2016年 | 283篇 |
2015年 | 449篇 |
2014年 | 439篇 |
2013年 | 574篇 |
2012年 | 651篇 |
2011年 | 625篇 |
2010年 | 342篇 |
2009年 | 311篇 |
2008年 | 391篇 |
2007年 | 369篇 |
2006年 | 335篇 |
2005年 | 303篇 |
2004年 | 258篇 |
2003年 | 211篇 |
2002年 | 234篇 |
2001年 | 41篇 |
2000年 | 28篇 |
1999年 | 41篇 |
1998年 | 53篇 |
1997年 | 28篇 |
1996年 | 34篇 |
1995年 | 23篇 |
1994年 | 28篇 |
1993年 | 22篇 |
1992年 | 27篇 |
1991年 | 16篇 |
1990年 | 16篇 |
1989年 | 14篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1986年 | 6篇 |
1985年 | 10篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1981年 | 8篇 |
1980年 | 14篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1974年 | 6篇 |
1973年 | 14篇 |
排序方式: 共有7338条查询结果,搜索用时 15 毫秒
911.
912.
Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism 总被引:6,自引:0,他引:6
Thommesen L Stunes AK Monjo M Grøsvik K Tamburstuen MV Kjøbli E Lyngstadaas SP Reseland JE Syversen U 《Journal of cellular biochemistry》2006,99(3):824-834
The adipose tissue is the site of expression and secretion of a range of biologically active proteins, called adipokines, for example, leptin, adiponectin, and resistin. Leptin has previously been shown to be expressed in osteoblasts and to promote bone mineralization, whereas adiponectin expression is enhanced during osteoblast differentiation. In the present study we explored the possible role of resistin in bone metabolism. We found that resistin is expressed in murine preosteoclasts and preosteoblasts (RAW 264.7, MC3T3-E1), in primary human bone marrow stem cells and in mature human osteoblasts. The expression of resistin mRNA in RAW 264.7 was increased during differentiation and seemed to be regulated through PKC- and PKA-dependent mechanisms. Recombinant resistin increased the number of differentiated osteoclasts and stimulated NFkappaB promoter activity, indicating a role in osteoclastogenesis. Resistin also enhanced the proliferation of MC3T3-E1 cells in a PKA and PKC-dependent manner, but only weakly interfered with genes known to be upregulated during differentiation of MC3T3-E1 into osteoblasts. All together, our results indicate that resistin may play a role in bone remodeling. 相似文献
913.
Marsh HN Dubreuil CI Quevedo C Lee A Majdan M Walsh GS Hausdorff S Said FA Zoueva O Kozlowski M Siminovitch K Neel BG Miller FD Kaplan DR 《The Journal of cell biology》2003,163(5):999-1010
Nerve growth factor (NGF) mediates the survival and differentiation of neurons by stimulating the tyrosine kinase activity of the TrkA/NGF receptor. Here, we identify SHP-1 as a phosphotyrosine phosphatase that negatively regulates TrkA. SHP-1 formed complexes with TrkA at Y490, and dephosphorylated it at Y674/675. Expression of SHP-1 in sympathetic neurons induced apoptosis and TrkA dephosphorylation. Conversely, inhibition of endogenous SHP-1 with a dominant-inhibitory mutant stimulated basal tyrosine phosphorylation of TrkA, thereby promoting NGF-independent survival and causing sustained and elevated TrkA activation in the presence of NGF. Mice lacking SHP-1 had increased numbers of sympathetic neurons during the period of naturally occurring neuronal cell death, and when cultured, these neurons survived better than wild-type neurons in the absence of NGF. These data indicate that SHP-1 can function as a TrkA phosphatase, controlling both the basal and NGF-regulated level of TrkA activity in neurons, and suggest that SHP-1 regulates neuron number during the developmental cell death period by directly regulating TrkA activity. 相似文献
914.
Pollero Ricardo J. Gaspar María L. Cabello Marta 《World journal of microbiology & biotechnology》2001,17(8):805-810
Several properties of the lipolytic activity exhibited by the conidial fungus Phoma glomerata were studied. Lipolytic activity in an aqueous buffer medium was measured on triacylglycerol, phosphoglyceride and cholesterol ester under different experimental conditions. The effect of storage temperature on the stability of the hydrolytic activity, and optimal conditions of temperature and time of maximal activity were determined. The optimal conditions for maximal lipolytic activity were found to be 40–50 °C and 1 h. The activity released to the medium by 1 mg cells for 1 h at 40 °C was stated as the enzyme released unit (ERU). The protein fraction of MW > 50 kDa obtained by ultrafiltration of the medium, was active on the three substrates assayed, and it showed a non-specific hydrolytic activity on both the 1- and 2-acyl esters either in the neutral glyceride or in the phosphoglyceride. A protein of M
r approx. 75 kDa was the only one that showed esterase activity. The crude medium, stored at –15 °C, maintained its initial hydrolytic activity on triacylglycerol for at least 42 days, though when it was kept for 10 days at 4 °C, the activity fell to 50%. Kinetic parameters using substrates such as triolein (TO), dipalmitoyl phosphatidylcholine (DPPC) and cholesteryl oleate (ChoO), were comparatively evaluated. The activity of the enzyme in the hydrolysis of TO showed the highest values, whereas the maximal specific activities were less when the enzyme was assayed against DPPC and ChoO. 相似文献
915.
Marta Wrzosek Małgorzata Ruszkiewicz-Michalska Katarzyna Sikora Marta Damszel Zbigniew Sierota 《Mycological Progress》2017,16(2):101-108
Their hyphal structure, the common events of hybridization and horizontal gene transfer, as well as intimate associations with prokaryotes (including endobiotic bacteria) and cooperation with eukaryotes have made fungi very flexible at the genetic, physiological, and ecological levels. It is manifested with the fungal ability to perfectly exploit existing nutrient sources and plastically fit into a changing environment. Although the links between fungi and other ecosystem components are rarely clearly visible and unambiguous, fungi can be ecosystem buffers playing a homeostatic role throughout global ecosystems, reacting to changes in various ways, not only by modifications of gene expression but also by nuclear status and “extended phenotype”. The goal of this review is to underline some ecological interactions involving fungi and other organisms and to indicate high fungal plasticity in terms of ontogenetic perspective. 相似文献
916.
Cappellozza S Saviane A Tettamanti G Squadrin M Vendramin E Paolucci P Franzetti E Squartini A 《Journal of invertebrate pathology》2011,106(3):386-393
Enterococcus mundtii was shown to be directly correlated with flacherie disease of the silkworm larvae reared on artificial diet supplemented with chloramphenicol. Its identification was carried out by means of light and electron microscopy and nucleotide sequencing of 16S gene. The bacterium is capable of rapidly multiplying in the silkworm gut and of invading other body tissues, as demonstrated by deliberate infection of germfree larvae and by subsequent TEM observations. E. mundtii can endure alkaline pH of the silkworm gut and it has been proved to adapt in vitro to commonly applied doses of chloramphenicol, whose use can further contribute to reduce competition by other bacteria in Bombyx mori alimentary canal.The modality of transmission of the infection to the larvae was among the objectives of the present research. Since contamination of the progeny by mother moths can be avoided through routine egg shell disinfection, a trans-ovarian vertical transmission can be ruled out. On the other hand the bacterium was for the first time identified on mulberry leaves, and therefore artificial diet based on leaf powder could be a source of infection. We showed that while microwaved diet could contain live E. mundtii cells, the autoclaved diet is safe in this respect. Being E. mundtii also part of the human-associated microbiota, and since B. mori is totally domestic species, a possible role of man in its epidemiology can be postulated. 相似文献
917.
918.
Johannes G. Achatz Marta Chiodin Willi Salvenmoser Seth Tyler Pedro Martinez 《Organisms Diversity & Evolution》2013,13(2):267-286
Acoels are among the simplest worms and therefore have often been pivotal in discussions of the origin of the Bilateria. Initially thought primitive because of their “planula-like” morphology, including their lumenless digestive system, they were subsequently dismissed by many morphologists as a specialized clade of the Platyhelminthes. However, since molecular phylogenies placed them outside the Platyhelminthes and outside all other phyla at the base of the Bilateria, they became the focus of renewed debate and research. We review what is currently known of acoels, including information regarding their morphology, development, systematics, and phylogenetic relationships, and put some of these topics in a historical perspective to show how the application of new methods contributed to the progress in understanding these animals. Taking all available data into consideration, clear-cut conclusions cannot be made; however, in our view it becomes successively clearer that acoelomorphs are a “basal” but “divergent” branch of the Bilateria. 相似文献
919.
Xavier Solé Marta Crous-Bou David Cordero David Olivares Elisabet Guinó Rebeca Sanz-Pamplona Francisco Rodriguez-Moranta Xavier Sanjuan Javier de Oca Ramon Salazar Victor Moreno 《PloS one》2014,9(9)
Background
Accurate detection of characteristic proteins secreted by colon cancer tumor cells in biological fluids could serve as a biomarker for the disease. The aim of the present study was to identify and validate new serum biomarkers and demonstrate their potential usefulness for early diagnosis of colon cancer.Methods
The study was organized in three sequential phases: 1) biomarker discovery, 2) technical and biological validation, and 3) proof of concept to test the potential clinical use of selected biomarkers. A prioritized subset of the differentially-expressed genes between tissue types (50 colon mucosa from cancer-free individuals and 100 normal-tumor pairs from colon cancer patients) was validated and further tested in a series of serum samples from 80 colon cancer cases, 23 patients with adenoma and 77 cancer-free controls.Results
In the discovery phase, 505 unique candidate biomarkers were identified, with highly significant results and high capacity to discriminate between the different tissue types. After a subsequent prioritization, all tested genes (N = 23) were successfully validated in tissue, and one of them, COL10A1, showed relevant differences in serum protein levels between controls, patients with adenoma (p = 0.0083) and colon cancer cases (p = 3.2e-6).Conclusion
We present a sequential process for the identification and further validation of biomarkers for early detection of colon cancer that identifies COL10A1 protein levels in serum as a potential diagnostic candidate to detect both adenoma lesions and tumor.Impact
The use of a cheap serum test for colon cancer screening should improve its participation rates and contribute to decrease the burden of this disease. 相似文献920.