全文获取类型
收费全文 | 1171篇 |
免费 | 183篇 |
专业分类
1354篇 |
出版年
2022年 | 10篇 |
2021年 | 21篇 |
2020年 | 14篇 |
2019年 | 19篇 |
2018年 | 21篇 |
2017年 | 25篇 |
2016年 | 27篇 |
2015年 | 41篇 |
2014年 | 38篇 |
2013年 | 55篇 |
2012年 | 62篇 |
2011年 | 54篇 |
2010年 | 31篇 |
2009年 | 33篇 |
2008年 | 51篇 |
2007年 | 40篇 |
2006年 | 44篇 |
2005年 | 41篇 |
2004年 | 45篇 |
2003年 | 41篇 |
2002年 | 33篇 |
2001年 | 31篇 |
2000年 | 46篇 |
1999年 | 29篇 |
1998年 | 14篇 |
1997年 | 9篇 |
1996年 | 10篇 |
1992年 | 11篇 |
1991年 | 26篇 |
1990年 | 19篇 |
1989年 | 19篇 |
1988年 | 21篇 |
1987年 | 24篇 |
1986年 | 16篇 |
1985年 | 17篇 |
1984年 | 13篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1980年 | 11篇 |
1979年 | 13篇 |
1975年 | 9篇 |
1974年 | 12篇 |
1973年 | 13篇 |
1972年 | 11篇 |
1971年 | 19篇 |
1970年 | 8篇 |
1969年 | 8篇 |
1968年 | 8篇 |
1967年 | 9篇 |
1966年 | 8篇 |
排序方式: 共有1354条查询结果,搜索用时 15 毫秒
71.
M Parry-Billings B Leighton G D Dimitriadis R Curi J Bond S Bevan A Colquhoun E A Newsholme 《The International journal of biochemistry》1991,23(9):933-937
1. The effects of tumour bearing on glutamine metabolism in rat skeletal muscle were examined using the Walker 256 carcinosarcoma. 2. There was a rapid and marked decrease in skeletal muscle glutamine content, which was correlated with the size of the tumour, and a decrease in plasma glutamine concentration. 3. The rate of release of glutamine from EDL muscle in vitro was increased in cachectic, tumour bearing animals, but was unaffected from the soleus muscle of the same animals. 4. It is hypothesized that the increase in the rate of muscle glutamine release during cachexia represents a response of this tissue in order to satisfy the demand for glutamine by the tumour or by cells of the immune system. 相似文献
72.
Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity 总被引:1,自引:0,他引:1
Bertenshaw GP Turk BE Hubbard SJ Matters GL Bylander JE Crisman JM Cantley LC Bond JS 《The Journal of biological chemistry》2001,276(16):13248-13255
Meprin A and B are highly regulated, secreted, and cell-surface metalloendopeptidases that are abundantly expressed in the kidney and intestine. Meprin oligomers consist of evolutionarily related alpha and/or beta subunits. The work herein was carried out to identify bioactive peptides and proteins that are susceptible to hydrolysis by mouse meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide fragment 14-27 and gastrin 17, regulatory molecules of the gastrointestinal tract, were found to be the best peptide substrates for meprin A and B, respectively. Peptide libraries and a variety of naturally occurring peptides revealed that the meprin beta subunit has a clear preference for acidic amino acids in the P1 and P1' sites of substrates. The meprin alpha subunit selected for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues in the P1 and P1' sites, and proline was the most preferred amino acid at the P2' position. Thus, although the meprin alpha and beta subunits share 55% amino acid identity within the protease domain and are normally localized at the same tissue cell surfaces, they have very different substrate and peptide bond specificities indicating different functions. Homology models of the mouse meprin alpha and beta protease domains, based on the astacin crystal structure, revealed active site differences that can account for the marked differences in substrate specificity of the two subunits. 相似文献
73.
Meprins are secreted and membrane-bound metalloendopeptidases highly expressed in kidney and intestinal epithelial cells. They are oligomeric glycoproteins composed of evolutionarily related alpha and/or beta subunits. The present work revealed that the messages for both meprin subunits were expressed in intestine and kidney in ICR and C3H/He mouse embryos (as early as day 11), indicating developmental functions for both subunits. During the first 2 weeks after birth, the mRNA levels for both subunits increased in ICR mice, but between 10 days and 3 weeks (time of weaning) the alpha subunit level in the intestine fell markedly. In adult ICR mice, meprin beta mRNA was consistently expressed in both kidney and intestine, whereas meprin alpha mRNA was highly expressed in kidney but only present at low levels in intestine. In C3H/He mice, the pattern of meprin alpha and beta subunit mRNA expression was similar to that of ICR mice, except that meprin alpha was barely detectable in kidney after birth. The results of postnatal studies indicate that the meprin alpha subunit has a role in the intestine during suckling but is not essential after weaning, and that the beta homooligomer is the major meprin form after weaning in both kidney and intestine. 相似文献
74.
75.
Spinosad is a naturally derived biorational insecticide with an environmentally favourable toxicity profile, so we investigated its potency against mosquito larvae (Diptera: Culicidae). By laboratory bioassays of a suspension concentrate formulation of spinosad (Tracer), the 24 h lethal concentration (LC50) against Aedes aegypti (L.) third and fourth instars was estimated at 0.025 p.p.m. following logit regression. The concentration-mortality response of third- and fourth-instar Anopheles albimanus Weidemann did not conform to a logit model. The LC50 value of spinosad in Anopheles albimanus was 0.024 p.p.m. by quadratic linear regression. A field trial in southern Mexico demonstrated that spinosad 1 p.p.m. compared with the standard temephos (Abate) 1% granules 100 g/m3 water prevented Ae. aegypti breeding in plastic containers of water for 8 weeks; at 10 p.p.m. spinosad prevented breeding for > 22 weeks. In another field trial, spinosad at 5 p.p.m. and temephos both completely eliminated reproduction of Ae. aegypti for 13 weeks. In contrast, the bacterial insecticide Bacillus thuringiensis var. israelensis (Bti, Vectobac) AS) performed poorly with just 2 weeks of complete inhibition of Ae. aegypti breeding. Spinosad also effectively prevented breeding of Culex mosquitoes and chironomids in both trials to a degree similar to that of temephos. We conclude that spinosad merits evaluation as a replacement for organophosphate or Bti treatment of domestic water tanks in Mesoamerica. We also predict that spinosad is likely to be an effective larvicide for treatment of mosquito breeding sites. 相似文献
76.
Baker BJ Lutz MA Dawson SC Bond PL Banfield JF 《Applied and environmental microbiology》2004,70(10):6264-6271
Acid mine drainage (AMD) microbial communities contain microbial eukaryotes (both fungi and protists) that confer a biofilm structure and impact the abundance of bacteria and archaea and the community composition via grazing and other mechanisms. Since prokaryotes impact iron oxidation rates and thus regulate AMD generation rates, it is important to analyze the fungal and protistan populations. We utilized 18S rRNA and beta-tubulin gene phylogenies and fluorescent rRNA-specific probes to characterize the eukaryotic diversity and distribution in extremely acidic (pHs 0.8 to 1.38), warm (30 to 50 degrees C), metal-rich (up to 269 mM Fe(2+), 16.8 mM Zn, 8.5 mM As, and 4.1 mM Cu) AMD solutions from the Richmond Mine at Iron Mountain, Calif. A Rhodophyta (red algae) lineage and organisms from the Vahlkampfiidae family were identified. The fungal 18S rRNA and tubulin gene sequences formed two distinct phylogenetic groups associated with the classes Dothideomycetes and Eurotiomycetes. Three fungal isolates that were closely related to the Dothideomycetes clones were obtained. We suggest the name "Acidomyces richmondensis" for these isolates. Since these ascomycete fungi were morphologically indistinguishable, rRNA-specific oligonucleotide probes were designed to target the Dothideomycetes and Eurotiomycetes via fluorescent in situ hybridization (FISH). FISH analyses indicated that Eurotiomycetes are generally more abundant than Dothideomycetes in all of the seven locations studied within the Richmond Mine system. This is the first study to combine the culture-independent detection of fungi with in situ detection and a demonstration of activity in an acidic environment. The results expand our understanding of the subsurface AMD microbial community structure. 相似文献
77.
Circulating oxidized low-density lipoprotein and common carotid artery intima-media thickness in a random sample of middle-aged men 总被引:1,自引:0,他引:1
Metso S Loimaala A Mercuri MF Nenonen A Vuori I Oja P Bond MG Laine S Rontu R Lehtimäki T 《Journal of biomedical science》2004,11(3):356-361
Circulating oxidized low-density lipoprotein (oxLDL) has been suggested to play an important role in atherosclerosis development. According to previous observations, oxLDL correlates with clinically manifest coronary and carotid artery disease. We investigated the association between the oxLDL concentration measured directly in plasma and common carotid artery intima-media thickness (IMT) in a population-based, case-control study in middle-aged men from Southern Finland. oxLDL was determined in 214 men by a commercially available sandwich ELISA test (Mercodia). Carotid artery IMT was measured at 12 standardized segments by B-mode ultrasonography (at the near and far wall of the left and right common carotid arteries, bifurcations and internal carotid arteries), and the overall mean maximum IMT (MMaxIMT) was calculated. The MMaxIMT of the carotid arteries was significantly associated with circulating oxLDL (rs=0.16, p=0.018). In a stepwise multiple regression model with MMaxIMT as dependent variable and systolic blood pressure, smoking, oxLDL, HDL cholesterol and apolipoprotein B as covariates, systolic blood pressure (=0.22, p<0.001), oxLDL (=0.15, p=0.022) and smoking (=0.17, p=0.014) showed an independent association with IMT (R2=0.10, p<0.001). Our results show that oxLDL measured directly from plasma is independently associated with subclinical carotid artery atherosclerosis in middle-aged men. 相似文献
78.
Kantham L Kerr-Bayles L Godde N Quick M Webb R Sunderland T Bond J Walder K Augert G Collier G 《Biochemical and biophysical research communications》2003,304(1):125-129
Previously we found elevated beacon gene expression in the hypothalamus of obese Psammomys obesus. Beacon administration into the lateral ventricle of P. obesus stimulated food intake and body weight gain. In the current study we used yeast two-hybrid technology to screen for proteins in the human brain that interact with beacon. CLK4, an isoform of cdc2/cdc28-like kinase family of proteins, was identified as a strong interacting partner for beacon. Using active recombinant proteins and a surface plasmon resonance based detection technique, we demonstrated that the three members of this subfamily of kinases (CLK1, 2, and 4) all interact with beacon. Based on the known sequence and functional properties of beacon and CLKs, we speculate that beacon could either modulate the function of key regulatory molecules such as PTP1B or control the expression patterns of specific genes involved in the central regulation of energy metabolism. 相似文献
79.
Hussain S Assender JW Bond M Wong LF Murphy D Newby AC 《The Journal of biological chemistry》2002,277(30):27345-27352
80.
Meprin A and B are highly regulated, secreted and cell-surface homo- and hetero-oligomeric enzymes. Meprins are abundantly expressed in kidney and intestine. The multidomain alpha and beta subunits have high sequence identity, however they have very different substrate specificities, oligomerization potentials and are differentially regulated. Here we describe that meprin subunit activities are modulated differently by physico-chemical factors. Homo-oligomeric meprin B had an acidic pH optimum. The low pH protonation indicated the existence of at least two ionizable groups. An additional ionizable group generated a shoulder in the basic pH range. Homo-oligomeric meprin A had a neutral pH optimum and the activity curve revealed that two ionizable groups might be protonated at acidic pH similar to meprin B. Increasing the concentration of salt generally inhibited meprin B activity. Meprin A was inhibited at low salt concentrations but activated as salt was increased. This work has important implications in the elucidation of the catalytic mechanisms of meprins and other metalloproteases. In addition, the activity of meprin oligomers that arise in tissues will be affected by variations in pH and NaCl. This could have profound implications because meprins are exposed to a range of conditions in the extracellular milieu of renal and intestinal tissues and in inflammation and cancer. 相似文献