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31.
We have examined the role of the mammalian initiation factor eIF1 in the formation of the 40 S preinitiation complex using in vitro binding of initiator Met-tRNA (as Met-tRNA(i).eIF2.GTP ternary complex) to 40 S ribosomal subunits in the absence of mRNA. We observed that, although both eIF1A and eIF3 are essential to generate a stable 40 S preinitiation complex, quantitative binding of the ternary complex to 40 S subunits also required eIF1. The 40 S preinitiation complex contained, in addition to eIF3, both eIF1 and eIF1A in a 1:1 stoichiometry with respect to the bound Met-tRNA(i). These three initiation factors also bind to free 40 S subunits, and the resulting complex can act as an acceptor of the ternary complex to form the 40 S preinitiation complex (40 S.eIF3.eIF1.eIF1A.Met-tRNA(i).eIF2.GTP). The stable association of eIF1 with 40 S subunits required the presence of eIF3. In contrast, the binding of eIF1A to free 40 S ribosomes as well as to the 40 S preinitiation complex was stabilized by the presence of both eIF1 and eIF3. These studies suggest that it is possible for eIF1 and eIF1A to bind the 40 S preinitiation complex prior to mRNA binding. 相似文献
32.
Formoguanamine (2,4-diamino-s-triazine) was known to be an effective chemical agent in inducing blindness in poultry chicks,
but not in adult birds. The present study was undertaken to demonstrate the influences, if any, of this chemical on the visual
performance and retinal histology in an adult sub-tropical wild bird, the roseringed parakeet (Psittacula krameri). Formoguanamine (FG) hydrochloride was subcutaneously injected into adult parakeets at a dosage of 25 mg (dissolved in 0.75
ml physiological saline)/100 g body weight/day, for two consecutive days while the control birds were injected only with a
placebo. The effects were studied after 10, 20 and 30 days of the last treatment of FG. Within 24 h of the treatment of FG,
about 90% of the total birds exhibited lack of visual responses to any light stimulus and even absence of pupillary light
reactions. The remaining birds became totally blind on the day following the last injection of FG and remained so till the
end of investigation. At the microscopic level, conspicuous degenerative changes were noted in the outer pigmented epithelium
and the photoreceptive layer of rods and cones in the retinas of FG treated birds. A significant reduction in the thickness
of the outer nuclear layer was also found in the retinas of FG treated parakeets, compared to that in the control birds. However,
the inner cell layers of the retina in the control and FG administered parakeets were almost identical. It deserves special
mention that the effects of FG, noted after 30 days of last treatment, were not very different from those noted just after
10 days of treatment. Collectively, the results of the present investigation demonstrate that FG can be used as a potent pharmacological
agent for inducing irreversible blindness through selective damage in retinal tissue even in the adult wild bird, thereby
making FG treatment an alternative euthanasic device to a cumbersome, stressful, surgical method of enucleation of the ocular
system for laboratory studies. 相似文献
33.
Spinal fusions are being performed for various pathologies of the spine. Stabilizing vertebral segments by eliminating motion
across those segments becomes critical in dealing with pathologies of the spine that lead to instability. The use of autograft
has been the gold standard for spine fusion. However, due to complications such as donor site morbidity, increased operating
time, and limited supply, the use of allograft as a graft extender has become an acceptable practice especially in fusions
spanning multiple segments. The discovery and isolation of novel proteins (i.e., bone morphogenetic proteins, BMPs), which
initiate the molecular cascade of bone formation, have experimentally been shown in numerous animal studies to be as effective
as autografts. Although the use of BMPs has exciting applications in spine surgery, long-term clinical studies must be evaluated
for its efficacy in various applications in humans. The use of biomimetic materials such as hydroxyapatite (HA), or tricalcium
phosphate (TCP) has also been examined in several animal models as bone graft substitutes or carriers. Although these materials
have shown some promise in specific site applications, more work remains in elucidating an efficacious combination of these
materials and BMPs that can be as effective as autografts. This review will present the status of bone grafts, bone morphogenetic
proteins, gene therapy, and work that has been done to facilitate spinal fusion and simultaneously eliminate the need for
bone graft.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
34.
The synthesis of three novel phosphonobile acids from natural bile acids is reported. The CMC of phosphonodeoxycholic acid (PDCA) at pH 8.2 was found to be lower than that of the parent deoxycholic acid (DCA). PDCA micelles were also found to have higher microviscosity compared to DCA micelles, suggesting higher hydrophobicity and tighter packing in the interior of PDCA micelles. PDCA aggregated further to form an aqueous gel at pH 4. 相似文献
35.
Eukaryotic translation initiation factor 5 (eIF5) interacts with the 40S ribosomal initiation complex (40S.eIF3.AUG.Met-tRNA(f).eIF2.GTP) to promote the hydrolysis of bound GTP. In Saccharomyces cerevisiae, eIF5, a protein of 45346Da, is encoded by a single-copy essential gene, TIF5. In this paper, we have isolated a temperature-sensitive S. cerevisiae strain, TMY5-1, by replacing the wild-type chromosomal copy of TIF5 with one mutagenized in vitro. The mutant yeast cells rapidly cease protein synthesis when grown under non-permissive conditions, lose polyribosomes and accumulate free 80S ribosomes. Further characterization of mutant eIF5 showed that the mutant protein, expressed in Escherichia coli, is defective both in its interaction with eIF2 as well as in mediating the hydrolysis of GTP bound to the 40S initiation complex and consequently in the formation of the 80S initiation complex. Additionally, the availability of a yeast strain containing temperature-sensitive mutation in the eIF5 gene allowed us to construct a cell-free translation system that was dependent on exogenously added eIF5 for translation of mRNAs in vitro. 相似文献
36.
Prajna Gayen Sudipta Maitra Sutapa Datta Santi P. Sinha Babu 《Journal of biosciences》2010,35(1):73-77
Wolbachia are symbiotic endobacteria that infect the majority of filarial nematodes, including Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus. Recent studies have suggested that Wolbachia are necessary for the reproduction and survival of filarial nematodes and have highlighted the use of antibiotic therapy
such as tetracycline/doxycycline as a novel method of treatment for infections caused by these organisms. Before such therapy
is conceived and implemented on a large scale, it is necessary to assess the prevalence of the endosymbiont in W. bancrofti from different geographical locations. We present data from molecular and electron microscopic studies to provide evidence
for Wolbachia symbiosis in W. bancrofti microfilariae collected from two districts (Bankura and Birbhum) of West Bengal, India. 相似文献
37.
Synthesis, aggregation behavior and in vitro cholesterol solubilization studies of 16-epi-pythocholic acid (3α,12α,16β-trihydroxy-5β-cholan-24-oic acid, EPCA) are reported. The synthesis of this unnatural epimer of pythocholic acid (3α,12α,16α-trihydroxy-5β-cholan-24-oic acid, PCA) involves a series of simple and selective chemical transformations with an overall yield of 21% starting from readily available cholic acid (CA). The critical micellar concentration (CMC) of 16-epi-pythocholate in aqueous media was determined using pyrene as a fluorescent probe. In vitro cholesterol solubilization ability was evaluated using anhydrous cholesterol and results were compared with those of other natural di- and trihydroxy bile acids. These studies showed that 16-epi-pythocholic acid (16β-hydroxy-deoxycholic acid) behaves similar to cholic acid (CA) and avicholic acid (3α,7α,16α-trihydroxy-5β-cholan-24-oic acid, ACA) in its aggregation behavior and cholesterol dissolution properties. 相似文献
38.
The genome sequence of the cyanobacterium Synechocystis sp. PCC6803 revealed four Open reading frame (ORF) encoding putative inositol monophosphatase or inositol monophosphatase-like
proteins. One of the ORFs, sll1383, is ∼870 base pair long and has been assigned as a probable myo-inositol 1 (or 4) monophosphatase (IMPase; EC 3.1.3.25). IMPase is the second enzyme in the inositol biosynthesis pathway
and catalyses the conversion of L-myo-inositol 1-phosphate to free myo-inositol. The present work describes the functional assignment of ORF sll1383 as myo-inositol 1-phosphate phosphatase (IMPase) through molecular cloning, bacterial overexpression, purification and biochemical
characterization of the gene product. Affinity (K
m) of the recombinant protein for the substrate DL-myo-inositol 1-phosphate was found to be much higher (0.0034 ± 0.0003 mM) compared to IMPase(s) from other sources but in comparison
V
max (∼0.033 μmol Pi/min/mg protein) was low. Li+ was found to be an inhibitor (IC50 6.0 mM) of this enzyme, other monovalent metal ions (e.g. Na+, K+ NH4+) having no significant effect on the enzyme activity. Like other IMPase(s), the activity of this enzyme was found to be totally
Mg2+ dependent, which can be substituted partially by Mn2+. However, unlike other IMPase(s), the enzyme is optimally active at ∼42°C. To the best of our knowledge, sll1383 encoded
IMPase has the highest substrate affinity and specificity amongst the known examples from other prokaryotic sources. A possible
application of this recombinant protein in the enzymatic coupled assay of L-myo-inositol 1-phosphate synthase (MIPS) is discussed. 相似文献
39.
The physiological significance of melatonin in the regulation of annual testicular events in a major carp Catla catla was evaluated through studies on the effects of graded dose (25, 50, or 100 µg/100 g body wt.) of melatonin exogenously administered for different durations (1, 15, or 30 days) and manipulation of the endogenous melatonin system by exposing the fish to constant darkness (DD) or constant light (LL) for 30 days. An identical experimental schedule was followed during the preparatory (February-March), pre-spawning (April-May), spawning (July-August), and post-spawning (September-October) phases of the annual cycle. Irrespective of the reproductive status of the carp, LL suppressed while DD increased the mid-day and mid-night values of melatonin compared to respective controls. Influences of exogenous melatonin varied in relation to the dose and duration of treatment and the reproductive status of the carp. However, testicular response to exogenous melatonin (at 100 µg, for 30 days) and DD in each reproductive phase was almost identical. Notably, precocious testicular maturation occurred in both DD and melatonin-injected fish during the preparatory phase and in LL carps during the pre-spawning phase. In contrast, testicular functions in both the melatonin-treated and DD fish were inhibited during the pre-spawning and spawning phases, while the testes did not respond to any treatment during the post-spawning phase. In conclusion, this study provided the first experimental evidence that melatonin plays a significant role in the regulation of annual testicular events in a sub-tropical surface-dwelling carp Catla catla, but the influence of this pineal hormone on the seasonal activity of testis varies in relation to the reproductive status of the concerned fish. 相似文献
40.
Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging in experimental models of pancreatic cancer 总被引:3,自引:0,他引:3
Foss CA Fox JJ Feldmann G Maitra A Iacobuzio-Donohue C Kern SE Hruban R Pomper MG 《Molecular imaging》2007,6(2):131-139
Global expression profiling of pancreatic cancers has identified two cell surface molecules, claudin 4 and prostate stem cell antigen (PSCA), as being overexpressed in the vast majority of cases. Two antibodies, anti-claudin 4 and anti-PSCA, were radiolabeled with iodine 125 ((125)I) for imaging pancreatic cancer xenografts in mice using gamma scintigraphy and single-photon emission computed tomography-computed tomography (SPECT-CT). Immunofluorescence staining of intact and permeabilized Colo357 human pancreatic cancer cells showed strong extracellular staining by both anti-PSCA and anti-claudin 4. Biodistribution studies in claudin 4 and PSCA-expressing Colo357 and PANC-1 subcutaneous xenograft models in mice showed that [(125)I]anti-claudin 4 tumor to muscle ratio uptake was 4.3 in Colo357 at 6 days postinjection and 6.3 in PANC-1 xenografts at 4 days postinjection. Biodistribution of [(125)I]anti-PSCA showed tumor to muscle ratio uptake of 4.9 in Colo357 at 6 days postinjection. Planar gamma scintigraphic imaging in Colo357 xenograft-bearing mice showed clear tumor uptake of [(125)I]anti-claudin 4 by 24 hours postinjection and by 48 hours postinjection for [(125)I]anti-PSCA. SPECT-CT imaging with [(125)I]anti-claudin 4 and [(125)I]anti-PSCA in an L3.6PL orthotopic xenograft model showed strong tumor and spleen uptake at 5 days postinjection. Both anti-claudin 4 and anti-PSCA demonstrate promise as radiodiagnostic and possibly radiotherapeutic agents for human pancreatic cancers. 相似文献