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Agustin Guerrero-Hernández Daniel Leon-AparicioJesus Chavez-Reyes Jesus A. Olivares-ReyesSilvia DeJesus 《Cell calcium》2014
The endoplasmic reticulum is the main intracellular Ca2+ store for Ca2+ release during cell signaling. There are different strategies to avoid ER Ca2+ depletion. Release channels utilize first Ca2+-bound to proteins and this minimizes the reduction of the free luminal [Ca2+]. However, if release channels stay open after exhaustion of Ca2+-bound to proteins, then the reduction of the free luminal ER [Ca2+] (via STIM proteins) activates Ca2+ entry at the plasma membrane to restore the ER Ca2+ load, which will work provided that SERCA pump is active. Nevertheless, there are several noxious conditions that result in decreased activity of the SERCA pump such as oxidative stress, inflammatory cytokines, and saturated fatty acids, among others. These conditions result in a deficient restoration of the ER [Ca2+] and lead to the ER stress response that should facilitate recovery of the ER. However, if the stressful condition persists then ER stress ends up triggering cell death and the ensuing degenerative process leads to diverse pathologies; particularly insulin resistance, diabetes and several of the complications associated with diabetes. This scenario suggests that limiting ER stress should decrease the incidence of diabetes and the mobility and mortality associated with this illness. 相似文献
5.
《Bioorganic & medicinal chemistry》2014,22(21):6174-6182
Upon reacting 3′,4′-unsaturated cytosine (8 and 9) and adenine nucleosides (13 and 14) with XeF2/BF3·OEt2, the respective novel 3′,4′-difluoro-3′-deoxyribofuranosyl nucleosides (10–12 and 15–18) could be obtained. Formation of anti-adducts (11, 16 and 18) revealed that the fluorination involved oxonium ions as incipient intermediates. TBDMS-protected 3′,4′-unsaturated adenosine provided the β-face adducts as sole stereoisomers whereas α-face-selectivity was observed with the TBDPS-protected adenosine 14. The evaluation of the novel 3′-deoxy-3′,4′-difluororibofuranosylcytosine-(19–21) and adenine nucleosides (22–25) against antitumor and antiviral activities revealed that 3′,4′-difluorocordycepin (24) was found to possess anti-HCV activity. The SI of 24 was comparable to that of the anti-HCV drug ribavirin. However, sofosbuvir, FDA-approved novel anti-HCV drug, showed better SI value. Our finding revealed that the introduction of the fluoro-substituent into the 4′-position of cordycepin derivatives decreased the cytotoxicity to the host cell with retention of the antiviral activity. 相似文献
6.
Folsomia Candida was maintained on potato dextrose agar (PDA) plates precolonised by the mycoparasite Coniothyrium minitans for 3 yr but the sciarid Bradysia sp. survived for a maximum of only three generations. Collembolans and sciarid larvae from these cultures were able to transmit C. minitans to uninoculated PDA plates through the survival of spores in faecal pellets. Adult and larval sciarids also transmitted C. minitans from PDA culture to uninoculated PDA plates by contamination on the cuticle. In soil and sand both sciarids and collembolans were able to transmit C. minitans from C. m/m'tans-inoculated to uninoculated sclerotia of Sclerotinia sclerotiorum. Inoculation of sclerotia with C. minitans enabled greater populations of larger collembolans to develop. In the glasshouse where C. minitans had been applied to the soil, one adult sciarid and four collembolans out of 70 and 101 insects collected respectively yielded C. minitans on placement onto PDA + Aureomycin. 相似文献
7.
Prasert Akkaramongkolporn Tanasait Ngawhirunpat Praneet Opanasopit 《AAPS PharmSciTech》2009,10(2):641-648
The differently sulfonated styrene–divinylbenzene cross-linked copolymer cationic exchange resins were prepared by oil-in-water
polymerization and varied degrees of sulfonation. Several characteristics of the obtained resins were evaluated, i.e., Fourier
transform infrared spectra, the ion-exchange capacity, microscopic morphology, size, and swelling. The resin characteristics
were altered in relation to the degree of sulfonation, proving that differently sulfonated resins could be prepared. The behavior
of chlorpheniramine (CPM) loading and in vitro release in the USP simulated gastric (SGF) and intestinal fluids (SIF) of the obtained resins were also evaluated. The CPM
loaded in the resinates (drug-loaded resins) increased with the increasing degree of sulfonic group and hence the drug binding
site in the employed resins. The CPM release was lower from the resins with the higher degree of sulfonic group due to the
increase in the diffusive path depth. The CPM release was obviously lower in SGF than SIF because CPM, a weak base drug, ionized
to a greater extent in SGF and then preferred binding with rather than releasing from the resins. In conclusion, the differently
sulfonated resins could be utilized as novel carriers for drug delivery. 相似文献
8.
Adenosine and Glutamate Modulate Each Other's Release from Rat Hippocampal Synaptosomes 总被引:4,自引:3,他引:1
Abstract: In rat hippocampal synaptosomes, adenosine decreased the K+ (15 mM) or the kainate (1 mM) evoked release of glutamate and aspartate. An even more pronounced effect was observed in the presence of the stable adenosine analogue, R-phenylisopropyladenosine. All these effects were reversed by the selective adenosine A1 receptor antagonist 8-cyclo-pentyltheophylline. In the same synaptosomal preparation, K+ (30 mM) strongly stimulated the release of the preloaded [3H]adenosine in a partially Ca2+-dependent and tetrodotoxin (TTX)-sensitive manner. Moreover, in the same experimental conditions, both l -glutamate and l -aspartate enhanced the release of [3H]adenosine derivatives ([3H]ADD). The gluta-mate-evoked release was dose dependent and appeared to be Ca2+ independent and tetrodotoxin insensitive. This effect was not due to metabolism because even the nonmetabolizable isomers d -glutamate and d -aspartate were able to stimulate [3H]ADD release. In contrast, the specific glutamate agonists N-methyl-d -aspartate, kainate, and quisqualate failed to stimulate [3H]ADD release, suggesting that glutamate and aspartate effects were not mediated by known excitatory amino acid receptors. Moreover, NMDA was also ineffective in the absence of Mg2+ and l -glutamate-evoked release was not inhibited by adding the specific antagonists 2-amino-5-phosphonovaleric acid or 6–7-dinitroquinoxaline-2, 3-dione. The stimulatory effect did not appear specific for only excitatory amino acids, as γ-anunobutyric acid stimulated [3H]ADD release in a dose-related manner. These results suggest that, at least in synaptosomal preparations from rat hippocampus, adenosine and glutamate modulate each other's release. The exact mechanism of such interplay, although still, unknown, could help in the understanding of excitatory amino acid neurotoxicity. 相似文献
9.
Dirk Schäfer Markus Ebert Ralf Köber Volkmar Plagentz Andreas Dahmke 《Bioremediation Journal》2006,10(1-2):71-82
Oxygen release compounds (ORC) are one possibility to enhance aerobic degradation in contaminated aquifers. However, some applications have been reported where oxygen concentrations did not meet expectations, this was attributed to ground water composition, e.g., high pH. Column experiments have been performed and the measurements were interpreted using a numerical model to investigate oxygen release kinetics from ORC in more detail. Because the zero-order rate law recommended by the manufacturer did not reflect the measurements, a more complex kinetic scheme was developed. The simulations show a minor influence of inorganic ground water constituents on oxygen release from ORC in the columns due to buffering by mineral precipitation, but an enhanced oxygen release if aerobic degradation takes place. If ORC is applied as socks, the impact of inorganic ground water composition increases compared to the application in column experiments. A simple quadratic equation is provided to estimate oxygen release rate from the buffer capacity of the ground water versus increasing pH—a parameter easily determinable in the laboratory. For slightly mineralized waters with high pH, this equation forecasts decreased oxygen release, but no total inhibition of oxygen release. 相似文献
10.
《Bioorganic & medicinal chemistry》2016,24(2):294-303
New cyclic RGD peptide-anticancer agent conjugates, with different chemical functionalities attached to the parent peptide were synthesized in order to evaluate their biological activities and to provide a comparative study of their drug release profiles. The Integrin binding c(RGDfK) penta-peptide was used for the synthesis of Camptothecin (CPT) carbamate and Chlorambucil (CLB) amide conjugates. Substitution of the amino acid Lys with Ser resulted in a modified c(RGDfS) with a new attachment site, which enabled the synthesis of an ester CLB conjugate. Functional versatility of the conjugates was reflected in the variability of their drug release profiles, while the conserved RGD sequence of a selective binding to the αv integrin family, likely preserved their recognition by the Integrin and consequently their favorable toxicity towards targeted cancer cells. This hypothesis was supported by a computational analysis suggesting that all conjugates occupy conformational spaces similar to that of the Integrin bound bio-active parent peptide. 相似文献