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22.
Narges Abdali Enrico Barth Amir Norouzy Robert Schulz Werner M. Nau Ulrich Kleinekath?fer Andreas Tauch Roland Benz 《PloS one》2013,8(10)
Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed. 相似文献
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24.
Abdul Wadood Muhammad Riaz Amir ul Mulk Momin Khan Sobia Ahsan Haleem Sulaiman Shams Sahib Gul Ayaz Ahmed Muhammad Qasim Farman Ali Zaheer Ul-Haq 《Bioinformation》2014,10(5):299-307
Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically
considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and
medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several
computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of
known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP)
urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy
minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics
generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution
of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands..
The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the
reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different
groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as
urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully
identify potential drug candidates. 相似文献
25.
Beta-subunit of cardiac Na+-K+-ATPase dictates the concentration of the functional enzyme in caveolae 总被引:1,自引:0,他引:1
Previous studies showed the presence of a significant fraction of Na+-K+-ATPase -subunits in cardiac myocyte caveolae, suggesting the caveolar interactions of Na+-K+-ATPase with its signaling partners. Because both - and -subunits are required for ATPase activity, to clarify the status of the pumping function of caveolar Na+-K+-ATPase, we have examined the relative distribution of two major subunit isoforms (1 and 1) in caveolar and noncaveolar membranes of adult rat cardiac myocytes. When cell lysates treated with high salt (Na2CO3 or KCl) concentrations were fractionated by a standard density gradient procedure, the resulting light caveolar membranes contained 3040% of 1-subunits and 8090% of 1-subunits. Use of Na2CO3 was shown to inactivate Na+-K+-ATPase; however, caveolar membranes obtained by the KCl procedure were not denatured and contained 75% of total myocyte Na+-K+-ATPase activity. Sealed isolated caveolae exhibited active Na+ transport. Confocal microscopy supported the presence of ,-subunits in caveolae, and immunoprecipitation showed the association of the subunits with caveolin oligomers. The findings indicate that cardiac caveolar inpocketings are the primary portals for active Na+-K+ fluxes, and the sites where the pumping and signaling functions of Na+-K+-ATPase are integrated. Preferential concentration of 1-subunit in caveolae was cell specific; it was also noted in neonatal cardiac myocytes but not in fibroblasts and A7r5 cells. Uneven distributions of 1 and 1 in early and late endosomes of myocytes suggested different internalization routes of two subunits as a source of selective localization of active Na+-K+-ATPase in cardiac caveolae. cardiac myocyte; caveolin; oligomer; ouabain; sodium pump 相似文献
26.
Naeema A. Akbar Abdullah M. Assiri Omima I. Shabouni Osama M. Alwafi Rajaa Al-Raddadi Mohamad H. Alzahrani Esam I. Azhar Ashraf Amir Abdullah M. Aljiffri Abdulhakeem O. Althaqafi 《PLoS neglected tropical diseases》2020,14(11)
Rapid urbanization, global trade, and the exceptionally great numbers of worldwide visitors during Hajj and Umrah have all placed the Kingdom of Saudi Arabia at a significant risk of introducing several vector-borne tropical diseases, such as dengue fever virus (DENV) infection. In this study we estimated DENV infection cost of illness (COI) in Saudi Arabia in the period 2013–2017, by processing national data including all declared cases recorded in referral centers in the western region, being the endemic region of the country. Using a statistically validated predictive model that was built on a representative sample of 717 laboratory-confirmed cases of DENV infection, direct costs, due to care-related expenditures, were estimated by applying the predictive equation to national data. However, indirect costs, which are due to productivity loss, were estimated using the human capital model based on gross domestic product adjusted for invalidity duration. Further, under-reporting was adjusted by using an expansion factor EF = 3. We observed highest estimated costs in 2016 with over US$168.5 Million total costs, including direct (US$29.0 Million) and indirect (US$139.5 Million) costs, for a total 4415 confirmed cases. The total DENV COI for the five years was estimated as US$551.0 Million for a total 15,369 patients (59.7%) out of 25,745 declared cases, resulting in an average cost of US$11 947.6 by patient. Depending on the year, productivity years loss costs accounted for 63.3% to 83.8% of the estimated total costs. Dengue has a substantial local economic burden that costs US$110.2 Million per year, stressing the urgent need for an effective national prevention strategy to perform considerable cost-savings besides reducing morbidity. 相似文献
27.
Yaghoub Rahimi Amir Mehdizadeh Hojjatollah Nozad Charoudeh Mohammad Nouri Kobra Valaei Shabnam Fayezi Masoud Darabi 《Development, growth & differentiation》2015,57(9):667-674
Stearoyl‐CoA desaturase 1 (SCD1) plays important roles in organ development, glucose tolerance, insulin sensitivity, and cancer. Here, we examined the role of SCD1 for the differentiation of human induced pluripotent stem (hiPS) cells to liver cells by using drug inhibition and biochemical experiments. hiPS cells cultured in a pro‐hepatic medium were exposed to an SCD1 inhibitor at various stages throughout differentiation. Liver‐specific markers, specifically α‐fetoprotein, albumin and urea in conditioned medium, and hepatocyte nuclear factor 4α (HNF4α) and cytochrome P450 7A1 (CYP7A1) gene expressions and triglyceride in cellular extracts were analyzed at various development stages. Measures of hepatocyte‐specific function and triglyceride accumulation in later stages were strongly inhibited a minimum of −29% (P < 0.05) by SCD1 inhibitor in the early stage of hepatic differentiation and effectively reversed (>30%, P < 0.01) by the addition of oleate. The results were also reproducible with human primary mononuclear cells (hPMN). SCD1 inhibitor had no significant effect on liver‐specific markers when it was added in the hepatic maturation stage. However, it strikingly led to higher albumin (1.6‐fold, P = 0.03) and urea (1.9‐fold, P = 0.02) production, and HNF4α (1.9‐fold, P = 0.02) and CYP7A1 (1.3‐fold, P = 0.03) expression upon incubation during the lineage‐commitment stage. Hepatic differentiation from cultured hiPS cells is sensitive to SCD1 inhibition and this sensitivity is affected by the stage of cellular differentiation. Notably, findings also indicate that this notion can be extended to hPMN. The requirement for SCD1 activity in functional differentiation of hepatocytes may have relevance for human liver disease and metabolic dysregulation. 相似文献
28.
Abraham Amsterdam Avinoam Reches Yehudith Amir Yael Mintz Yoram Salomon 《Biochimica et Biophysica Acta (BBA)/General Subjects》1978,544(2):273-283
Heparin was found to be the most potent inhibitor of rat ovarian luteinizing hormone-sensitive adenylate cyclase (I50 = 2 μg/ml) when compared to other naturally occurring glycosaminoglycans. This inhinibition was also appparent when this enzyme was stimulated by follicle-stimulating hormone or prostaglandin E 2. Heparin was also found to inhibit glucagon-sensitive rat hepatice adenylate cyclase, and the prostaglandin E1-sensitive enzyme from rat ileum and human platelets. In contrast, heparin stimulated the dopamine sensitive adenylate cyclase from rat caudate nucleus. The sulfade polysugar dextran sulfate exerts similar effects on adenylate cyclase activity of the rat ovary was shown to inhibit hormone binding to rat ovarian plasma membrane in a manner similar to that exerted by heparin. In contrast to heparin, dextran sulfate inhibited dopamine-sensitive adenylate cyclase from rat caudate nucleus. 相似文献
29.
Lin Chung-Ying Cheng Andy S. K. Imani Vida Saffari Mohsen Ohayon Maurice M. Pakpour Amir H. 《Sleep and biological rhythms》2020,18(4):343-349
Sleep and Biological Rhythms - To examine the psychometric properties of the Sleep Condition Indicator (SCI) using different psychometric approaches [including classical test theory, Rasch models,... 相似文献
30.
Mirbolook Atena Rasouli-Sadaghiani MirHassan Sepehr Ebrahim Lakzian Amir Hakimi Mohammad 《Journal of Plant Growth Regulation》2021,40(2):831-847
Journal of Plant Growth Regulation - Plants require optimum amounts of nutrients for suitable growth and yield production. Accordingly, the most efficient methods of fertilization, including the... 相似文献