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51.
Rat CNS adenosine A2A receptors were studied after administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) by means of a quantitative autoradiographic method. Specific binding was quantified in striatum only. The highest density was found in caudate-putamen (2.50 fmol/mm2), followed by nuclei accumbens (1.85 fmol/mm2) and the lowest values in the olfactory tubercle (1.26 fmol/mm2). These differerences were statiscally significant. MP administration (150 mg/kg) caused significant increases (12–18%) in caudate-putamen and nuclei accumbens in both stages: seizure and postseizure and no changes in the olfactory tubercle. CPA administration (2 mg/kg) originated a rise of 16% in nuclei accumbens but no change in the other two regions. When CPA was injected 30 minutes before MP, an increase (18 to 45%) in caudate-putamen and nuclei accumbens at seizure and postseizure stages was observed. Saturation results, in striatal membrane fraction, indicate that receptor sites increased their maximal binding capacity (Bmax) while the apparent dissociation constant (Kd) remained unchanged. These results suggest the involvement of the adenosine A2A receptors in convulsant activity and that CPA administration at the dose selected brings about a rise in neuronal excitability in this area. 相似文献
52.
It has been 45 years since Russell and Burch first proposed the concept of the '3Rs', yet it remains unclear how those individuals involved in animal research view and implement these concepts. The authors used a questionnaire survey to determine how well-known experts judged issues related to the 3Rs. 相似文献
53.
LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons
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Rosso S Bollati F Bisbal M Peretti D Sumi T Nakamura T Quiroga S Ferreira A Cáceres A 《Molecular biology of the cell》2004,15(7):3433-3449
In this study, we examined the subcellular distribution and functions of LIMK1 in developing neurons. Confocal microscopy, subcellular fractionation, and expression of several epitope-tagged LIMK1 constructs revealed that LIMK1 is enriched in the Golgi apparatus and growth cones, with the LIM domain required for Golgi localization and the PDZ domain for its presence at neuritic tips. Overexpression of wild-type LIMK1 suppresses the formation of trans-Golgi derived tubules, and prevents cytochalasin D-induced Golgi fragmentation, whereas that of a kinase-defective mutant has the opposite effect. Transfection of wild-type LIMK1 accelerates axon formation and enhances the accumulation of Par3/Par6, insulin-like growth factor (IGF)1 receptors, and neural cell adhesion molecule (NCAM) at growth cones, while inhibiting the Golgi export of synaptophysin-containing vesicles. These effects were dependent on the Golgi localization of LIMK1, paralleled by an increase in cofilin phosphorylation and phalloidin staining in the region of the Golgi apparatus, and prevented by coexpression of constitutive active cofilin. The long-term overexpression of LIMK1 produces growth cone collapse and axon retraction, an effect that is dependent on its growth cone localization. Together, our results suggest an important role for LIMK1 in axon formation that is related with its ability to regulate Golgi dynamics, membrane traffic, and actin cytoskeletal organization. 相似文献
54.
Colotta V Catarzi D Varano F Filacchioni G Martini C Trincavelli L Lucacchini A 《Bioorganic & medicinal chemistry》2003,11(24):5509-5518
In previous papers (Colotta, V. et al. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 39. Colotta, V. et al. J. Med. Chem. 2000, 43, 1158) we reported the synthesis and binding affinity at bovine (b) A1 and A2A and human (h) A3 adenosine receptors (ARs) of the 4-amino-6-benzylamino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (compound A) which resulted in a potent and selective A2A AR antagonist. Compound A provided the lead compound of a series of 6- or 8-(hetero)arylalkylamino-4-amino-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives (compounds 1–20) which are the object of this paper. Most of the newly synthesized compounds are inactive at hA3 ARs while they possess both nanomolar bA2A affinities and different degrees of bA2A versus bA1 selectivity. The binding data show that hydrophilic substituents on the benzyl moiety are the most profitable for bA2A receptor affinity. Furthermore, their steric hindrance seems to play an important role for the bA2A AR interaction, thus suggesting that the 6-aralkylamino moiety of these ligands interacts with a size-limited binding pocket of this AR subtype. Thus, the SAR studies provided us some new insights about the structural requirements of the bA2A AR recognition site. 相似文献
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Castiglia R Corti M Colangelo P Annesi F Capanna E Verheyen W Sichilima AM Makundi R 《Hereditas》2003,139(2):81-89
Aethomys is a common and widespread rodent genus in the African savannas and grasslands. However, its systematics and taxonomy are still unclear as no study has covered the entire range. In fact it might not be a monophyletic genus and perhaps should be split into two subgenera, Micaelamys and Aethomys. In this paper, we present findings based on the cytogenetics and the entire cytochrome b sequence of two species from Zambia (A. kaiseri) and Tanzania (A. chrysophilus), and we compare them with the sequences of a South African species (A. namaquensis) and other allied muroid genera. Comparison of the banded chromosomes revealed complete G-band homology between the autosomes of the two species. However, the X and Y chromosomes clearly differ in size and in C- and G-banding, being much larger in A. kaiseri. Comparison of the cytochrome b sequences places the separation between A. kaiseri and A. chrysophilus at 4.49 Mya, a period of intense speciation in other African muroids. The resulting phylogeny strongly supports the idea of a paraphyletic group, suggesting the need to elevate the previously described subgenera to the genus rank. 相似文献
57.
Giancola C Petraccone L Pieri M De Napoli L Montesarchio D Piccialli G Barone G 《International journal of biological macromolecules》2001,28(5):5311-394
Differential scanning calorimetric (DSC), circular dichroism (CD) and molecular mechanics studies have been performed on two triple helices of DNA. The target duplex consists of 16 base pairs in alternate sequence of the type 5′-(purine)m(pyrimidine)m-3′. In both the triplexes, the third oligopyrimidine strand crosses the major groove at the purine–pyrimidine junction, with a simultaneous binding of the adjacent purine tracts on alternate strands of the Watson–Crick duplex. The switch is ensured by a non-nucleotide linker, the 1,2,3 propanetriol residue, that joins two 3′–3′ phosphodiester ends. The third strands differ from each other for a nucleotide in the junction region. The resulting triple helices were termed 14-mer-PXP and 15-mer-PXP (where P=phosphate and X=1,2,3-propanetriol residue) according to the number of nucleotides that compose the third strand. DSC data show two independent processes: the first corresponding to the dissociation of the third strand from the target duplex, the second to the dissociation of the double helix in two single strands. The two triple helices show the same stability at pH 6.6. At pH 6.0, the 15-mer-PXP triplex is thermodynamically more stable than the 14-mer-PXP triplex. Thermodynamic data are discussed in relation to structural models. The results are useful when considering the design of oligonucleotides that can bind in an antigene approach to the DNA for therapeutic purposes. 相似文献
58.
Quartacci MF Glisić O Stevanović B Navari-Izzo F 《Journal of experimental botany》2002,53(378):2159-2166
Plants of Ramonda serbica were dehydrated to 3.6% relative water content (RWC) by withholding water for 3 weeks, afterwards the plants were rehydrated for 1 week to 93.8% RWC. Plasma membranes were isolated from leaves using a two-phase aqueous polymer partition system. Compared with well-hydrated (control) leaves, dehydrated leaves suffered a reduction of about 75% in their plasma membrane lipid content, which returned to the control level following rewatering. Also the lipid to protein ratio decreased after dehydration, almost regaining the initial value after rehydration. Lipids extracted from the plasma membrane of fully-hydrated leaves were characterized by a high level of free sterols and a much lower level of phospholipids. Smaller amounts of cerebrosides, acylated steryl glycosides and steryl glycosides were also detected. The main phospholipids of control leaves were phosphatidylcholine and phosphatidylethanolamine, whereas sitosterol was the free sterol present in the highest amount. Following dehydration, leaf plasma membrane lipids showed a constant level of free sterols and a reduction in phospholipids compared with the well-hydrated leaves. Both phosphatidylcholine and phosphatidylethanolamine decreased following dehydration, their molar ratio remaining unchanged. Among free sterols, the remarkably high cholesterol level present in the control leaves (about 14 mol%) increased 2-fold as a result of dehydration. Dehydration caused a general decrease in the unsaturation level of individual phospholipids and total lipids as well. Upon rehydration the lipid composition of leaf plasma membranes restored very quickly approaching the levels of well-hydrated leaves. 相似文献
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60.
Pieri Pde C Pereira DH Glina S Hallak J McElreavey K Moreira-Filho CA 《Genetic testing》2002,6(3):185-194
PCR-based screening of microdeletions in the azoospermic factor (AZF) on the Yq chromosome is an accepted means of identifying a common genetic cause of male infertility, responsible for 5-15% of cases associated with a low sperm count (=5 x 10(6) sptz/ml). Based on an extensive analysis of the literature, we have established a cost-effective preliminary PCR-based diagnostic screening test, with a set of six pairs of primers ("set-of-6") that have the capability of detecting up to 95% of the Y microdeletion cases already published. These primers are: sY84 in AZFa, sY114, sY129, sY143 in AZFb, and sY149, sY254 in AZFc. Initially, the set-of-6 was tested with 13 other pairs of primers covering the three AZF subregions. A sample of 114 infertile men was tested and 10 (8.8%) microdeletions were found, 3 of which were among the 26 (11.5%) idiopathic azoospermic men. These results showed that all detected microdeletions would be identified using the set-of-6 only. Another sample of 34 patients was subsequently tested using the set-of-6 and 3 (8.8%) microdeletions were found in this group. A comparison of our results with those reported in the literature showed similar microdeletion detection frequencies, demonstrating that the set-of-6 primers provides a reliable, simple and cost-effective way of detecting AZF deletions. 相似文献