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161.
Naik H Wei SY Schmidt MS Murry DJ Fleckenstein L 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,853(1-2):80-87
A reliable method has been developed for the determination of pyronaridine in human urine using amodiaquine as an internal standard. Liquid-liquid extraction was used for sample preparation. Analysis was performed on a Shimadzu LCMS-2010 in single ion monitoring positive mode using atmospheric pressure chemical ionization (APCI) as an interface. The extracted ion for pyronaridine was m/z 518.20 and for amodiaquine was m/z 356.10. Chromatography was carried out using a Gemini 5 microm C18 3.0 mmx150 mm column using 2 mM perflurooctanoic acid and acetonitrile mixture as a mobile phase delivered at a flow rate of 0.5 mL/min. The mobile phase was delivered in gradient mode. The retention times of pyronaridine and amodiaquine were 9.1 and 8.1 min respectively, with a total run time of 14 min. The assay was linear over a range of 14.3-1425 ng/mL for pyronaridine (R2>or=0.992, weighted 1/Concentration). The analysis of quality control samples for pyronaridine at 28.5, 285, 684 and 1140 ng/mL demonstrated excellent precision with relative standard deviation of 5.1, 2.3, 3.9 and 9.2%, respectively (n=5). Recoveries at concentrations of 28.5, 285, 684 and 1140 ng/mL were all greater than 85%.This LC-MS method for the determination of pyronaridine in human urine has excellent specifications for sensitivity, reproducibility and accuracy and can reliably quantitate concentrations of pyronaridine in urine as low as 14.3 ng/mL. The method will be used to quantify pyronaridine in human urine for pharmacokinetic and drug safety studies. 相似文献
162.
Kang LI Wang Y Suckow AT Czymmek KJ Cooke VG Naik UP Duncan MK 《The international journal of biochemistry & cell biology》2007,39(3):576-585
Junctional adhesion molecule-A (JAM-A, JAM-1, F11R) is an Ig domain containing transmembrane protein that has been proposed to function in diverse processes including platelet activation and adhesion, leukocyte transmigration, angiogenesis, epithelial cell shape and endothelial cell migration although its function in vivo is less well established. In the mouse eye, JAM-A protein expression is first detected at 12.5 dpc in the blood vessels of the tunica vasculosa, while it is first detected in both the corneal epithelium and lens between 13.5 and 14.5 dpc. In the corneal epithelium, JAM-A levels remain appreciable throughout life, while JAM-A immunostaining becomes stronger in the lens as the animals age. Both the cornea and lens of mice lacking an intact JAM-A gene are transparent until at least a year of age, although the cells of the JAM-A null corneal epithelium are irregularly shaped. In wild-type mice, JAM-A protein is found at the leading edge of repairing corneal epithelial wounds, however, corneal epithelial wound repair was qualitatively normal in JAM-A null animals. In summary, JAM-A is expressed in the corneal epithelium where it appears to regulate cell shape. 相似文献
163.
S. K. Chakrabarti D. Pattanayak D. Sarkar V. P. Chimote P. S. Naik 《Biologia Plantarum》2006,50(4):531-536
Variations in random amplified polymorphic DNA (RAPD) profiles from leaf, stem, root, and tuber tissues were observed in case
of two glasshouse grown potato cultivars using 40 decamer primers suggesting possible danger of cultivar misidentification.
Genomic DNA extracted from the above four tissues of four in vitro grown potato cultivars, however, produced more uniform RAPD fingerprints. A significant effect of random primers on fingerprint
uniformity was observed in case of both glasshouse and in vitro grown samples. A new concept of stability index for random primers based on homogeneity of RAPD profiles obtained from different
tissues of a single plant have been introduced. It is concluded that RAPD analysis of genomic DNA extracted from any tissue
of in vitro grown potato plants using 14 selected decamer primers could be used to develop RAPD fingerprints for identification of Indian
potato cultivars. 相似文献
164.
Nieuwenhuizen L Khalil MK Venkatesh N Othman NH 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2006,28(2):87-96
OBJECTIVE: To determine the ideal histochemical stain to differentiate between non-neoplastic and neoplastic endocervix and endometrium. STUDY DESIGN: A total of 90 cases representing nonneoplastic cervix, non-neoplastic endometrium, endocervical adenocarcinoma and endometrial adenocarcinoma were stained with toluidine blue (TB); methylene blue (MB); mucicarmine (MUC); periodic acid-Schiff before and after diastase digestion (PAS, PAS-D); Alcian blue, pH 2.5 (AB); and periodic acid-Schiff after Alcian blue, pH 2.5 (PAB). Cases were blinded and randomly divided between two pathologists for evaluation of the staining and the staining distribution of the glandular epithelium by means of a 36-color scheme. RESULTS: The majority of non-neoplastic endocervix samples stained blue with MB (57%), fuchsia with MUC (70%), magenta with PAS (77%) and PAS-D (73%) and dark turquoise with AB (70%). The majority of non-neoplastic endometrium samples stained slate blue with TB (60%) and pink with PAS-D (53.3%). There is statistical difference (p < 0.05) in the color of the epithelium and secretions between the non-neoplastic cervix and endometrium. The malignant glands of endocervical origin could be differentiated significantly (p = 0.043) from non-neoplastic endocervical epithelium by MUC. The epithelium of the non-neoplastic endometrium is significantly differentiated from malignant endometrium using TB (p = 0.015) and MB (p = 0.038). Endocervical carcinoma could be significantly differentiated from endometrial carcinoma by MB. The staining in endocervical adenocarcinoma and endometrial carcinoma was predominantly present in both apical and cytoplasmic locations compared to their non-neoplastic counterparts (endocervix, p = 0.003; endometrium, p = 0.049). CONCLUSION: This study showed that a panel of histochemical stains could differentiate glandular cells of endocervical epithelium from endometrium. 相似文献
165.
Optimization of alkali-catalyzed transesterification of Pongamia pinnata oil for production of biodiesel 总被引:3,自引:0,他引:3
Studies were carried out on transesterification of Karanja oil with methanol for the production of biodiesel. The reaction parameters such as catalyst concentration, alcohol/oil molar ratio, temperature, and rate of mixing were optimized for production of Karanja oil methyl ester (KOME). The fatty acid methyl esters content in the reaction mixture were quantified by HPLC and 1H NMR method. The yield of methyl esters from Karanja oil under the optimal condition was 97-98%. 相似文献
166.
Boot JR Boulet SL Clark BP Cases-Thomas MJ Delhaye L Diker K Fairhurst J Findlay J Gallagher PT Gilmore J Harris JR Masters JJ Mitchell SN Naik M Simmonds RG Smith SM Richards SJ Timms GH Whatton MA Wolfe CN Wood VA 《Bioorganic & medicinal chemistry letters》2006,16(10):2714-2718
A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake. 相似文献
167.
Soma Sengupta Manju George Katharine K. Miller Khurram Naik Jonathan Chou Mary Ann Cheatham Peter Dallos Mayumi Naramura Hamid Band Jing Zheng 《The Journal of biological chemistry》2009,284(30):20121-20129
Cadherin 23 (CDH23), a transmembrane protein localized near the tips of hair cell stereocilia in the mammalian inner ear, is important for delivering mechanical signals to the mechano-electric transducer channels. To identify CDH23-interacting proteins, a membrane-based yeast two-hybrid screen of an outer hair cell (OHC) cDNA library was performed. EHD4, a member of the C-terminal EH domain containing a protein family involved in endocytic recycling, was identified as a potential interactor. To confirm the interaction, we first demonstrated the EHD4 mRNA expression in hair cells using in situ hybridization. Next, we showed that EHD4 co-localizes and co-immunoprecipitates with CDH23 in mammalian cells. Interestingly, the co-immunoprecipitation was found to be calcium-sensitive. To investigate the role of EHD4 in hearing, compound action potentials were measured in EHD4 knock-out (KO) mice. Although EHD4 KO mice have normal hearing sensitivity, analysis of mouse cochlear lysates revealed a 2-fold increase in EHD1, but no increase in EHD2 or EHD3, in EHD4 KO cochleae compared with wild type, suggesting that a compensatory increase in EHD1 levels may account for the absence of a hearing defect in EHD4 KO mice. Taken together, these data indicate that EHD4 is a novel CDH23-interacting protein that could regulate CDH23 trafficking/localization in a calcium-sensitive manner.Hair cells located in the mammalian inner ear transform mechanical stimuli into electrical signals that in turn facilitate neurotransmitter release onto auditory neurons. The key element in the transduction process is the mechano-electric transducer (MET)2 apparatus located near the top of the stereocilium. CDH23 is a single pass transmembrane protein with 27 extracellular cadherin repeats. It is one of the components of the tip-link (1, 2), which connects the top of a shorter stereocilium to the side of its taller neighbor (3). Vibrations of the basilar membrane of the inner ear ultimately result in deflection of the hair bundles, which modulates tension on the tip-link, thereby controlling the opening probability of cation-selective MET channels (3, 4). Cations, principally K+ and Ca2+, flow through the MET channels and ultimately change the membrane potential. A mutation in the gene encoding CDH23, the Usher syndrome type 1D factor (USH1D), causes deaf-blindness in humans (5). Several interacting partners of CDH23 have been reported and include another tip-link protein protocadherin 15 (6), a multi-PDZ domain-containing scaffold protein harmonin (7) and a stereociliary scaffolding protein MAGI-1 (8). Protocadherin 15 binds to CDH23 through its extracellular domains (6), whereas the cytoplasmic region of CDH23 interacts with MAGI-1 and harmonin through its PDZ domain-binding interfaces (PBI). Harmonin also associates with other USH1 factors like myosin VIIa, protocadherin 15, and sans (9). These findings indicate that harmonin bridges CDH23 to the cytoskeletal actin core of the stereocilium and is probably essential for the developmental differentiation of stereocilia (10–12). However, it is currently unknown how CDH23 is transported to the tip of stereocilia. To search for additional interacting partners of CDH23, we performed a membrane-based yeast two-hybrid assay, which identified EHD4 as a potential binding partner (13).EHD4 belongs to an evolutionarily conserved EH (Eps 15 homology) domain-containing protein family involved in endocytic trafficking and recycling. Four highly homologous members of this family, EHD1–4, are expressed in mammalian cells. They contain a single C-terminal EH domain, an N-terminal nucleotide-binding loop and a coiled-coil region responsible for oligomerization (14–16). Of the four EHD proteins EHD1 is the best characterized and is involved in regulating the recycling of membrane receptors including the transferrin receptor and the major histocompatibility complex class I (17, 18). EHD1 is also involved in controlling cholesterol recycling and homeostasis (19) and in facilitating endosome to Golgi retrieval (20). EHD3 appears to regulate receptor movements from the early endosome (EE) to the endocytic recycling compartment (ERC) and Golgi (21, 22). EHD2 was isolated from GLUT4-enriched fractions of adipocytes and was shown to regulate insulin-mediated translocation of GLUT4 to the plasma membrane (23, 24). Additionally, EHD2 is involved in the regulation of transferrin receptor internalization (23), recycling (25), and actin cytoskeleton rearrangement (23). EHD4, also called Pincher, was first reported as an extracellular matrix protein (26). Subsequent studies have shown this intracellular protein to be involved in the regulation of neurotrophin receptor TrkA endocytosis in pheochromocytoma (PC12) cells (27). It is also involved in interactions with the cell fate determinant, NUMB, and co-localizes with the small GTP-binding protein, Arf6 (28). Recently, Sharma et al. (29) showed that EHD4 regulates the exit of endocytic cargo from the early endosome toward both the recycling compartment and the late endocytic pathway. They also indicated that EHD4 and EHD1 interact transiently as most of the EHD4 resides on peripheral early endosomes, while EHD1 resides primarily on tubular recycling compartments. This partial overlap/association might be necessary for the transport of proteins through the early endosome to the ERC. Previously, George et al. (25) had also demonstrated that EHD4 interacts with EHD1 and its paralogs, which suggests cooperation and partial overlap of function between EHD4 and EHD1.Unlike other CDH23-binding proteins, EHD4 does not contain a PDZ domain that could bind to the PBI located in the cytoplasmic tail of CDH23. In addition, the cytoplasmic tail of CDH23 lacks an Asn-Pro-Phe (NPF) motif that could mediate an interaction with the EH domain of EHD4. Therefore, we proceeded to characterize the authenticity of interaction between EHD4 and CDH23 identified in yeast and mammalian cells, using both in vitro and in vivo methods. We verified the expression of EHD4 mRNA in mouse cochlea and investigated the physiological role of EHD4 protein in the cochlea using EHD4-KO mice. 相似文献
168.
Endophytic populations were isolated from 2400 segments of Oryza sativa collected from Bhadra River Project Area, Southern India during December 2005 (Winter) and April 2006 (Summer). Overall colonization rates from surface sterilized tissues were 40.3% in roots and 25.83% in leaves during winter season, 20.15% in roots and 8.66% in leaves during summer season. Nineteen different fungal taxa, a Streptomyces sp. and bacterial species were isolated. Streptomyces sp., Chaetomium globosum, Penicillium chrysogenum, Fusarium oxysporum and Cladosporium cladosporioides were dominant endophytes in this study. Frequency of colonization between the sites, seasons and rice varieties were found to differ significantly. Dual culture studies revealed that C. globosum, P. chrysogenum and Streptomyces sp. are suitable candidates for extraction of biologically active compounds. Rice harbors many endophytic organisms and some of them have antagonistic properties against fungal pathogens. 相似文献
169.
Leo I. Gordon Michael A. Burke Amareshwar T. K. Singh Sheila Prachand Elliot D. Lieberman Lin Sun Tejaswitha Jairaj Naik Sathyamangla V. Naga Prasad Hossein Ardehali 《The Journal of biological chemistry》2009,284(4):2080-2087
Overexpression of the receptor tyrosine kinase erbB2 (Her2 in humans) is
correlated with a poor prognosis in breast and ovarian cancers. Treatment with
trastuzumab (a monoclonal antibody against erbB2) improves survival; however,
it also causes cardiomyopathy. We hypothesized that blockade of the erbB2
receptor induces cardiomyocyte death through a mitochondrial pathway that is
dependent on the production of reactive oxygen species (ROS). We first showed
that levels of erbB2 receptor are significantly decreased in an animal model
of ischemic heart disease and in human ischemic cardiomyopathy. We treated
neonatal rat cardiomyocytes with an inhibitory erbB2 antibody to study the
mechanism behind the deleterious effects of erbB2 blockade. These cells
displayed a dose-dependent increase in ROS production and cell death compared
with control IgG-treated cells; these processes were reversed by the
antioxidant, N-acetylcysteine. The effects of erbB2 antibody on both
cell death and ROS production were also reversed by cyclosporine A and
diazoxide, chemicals that regulate the pro- and anti-apoptotic channels in the
mitochondria, respectively. Furthermore, mouse embryonic fibroblasts lacking
Bax and Bak (proteins that mediate cell death through a mitochondrial pathway)
were resistant to the deleterious effects of erbB2 antibody. These effects of
erbB2 blockade appear to occur through a pathway involving AKT and
PKC-α. Our results suggest that erbB2 plays a role in cardiomyocyte
survival, and that the deleterious effects of trastuzumab on the heart occur
through a mitochondrial pathway and is mediated by ROS production.
Manipulation of redox signaling may be beneficial in cancer patients receiving
trastuzumab.The Her-2/neu oncogene, also known as erbB2 in nonhuman organisms, is a
transmembrane receptor tyrosine kinase that belongs to the epidermal growth
factor receptor family (1,
2). Overexpression of Her2 is
seen in ∼30% of breast cancer patients and is associated with poor
survival, increased metastasis, and resistance to chemotherapy
(3–5).
Transgenic mice overexpressing erbB2 develop focal mammary tumors, thus
implicating this protein in tumorigenesis
(6). Trastuzumab (Herceptin,
Genentech, CA) is a monoclonal antibody
(Ab)2 that binds to
Her2 with high affinity and improves survival of patients with advanced breast
cancer (7). Trastuzumab is
clinically efficacious both as a single agent or in combination with standard
chemotherapy regimens
(4–6).
However, this agent is cardiotoxic on its own, and especially when
administered with anthracyclines, where it can cause cardiomyopathy (CM) in up
to 27% of patients (8).The importance of erbB2 in normal cardiac development and physiology was
demonstrated in mice by cardiac-specific knock-out of erbB2
(9,
10). The mice were initially
normal, but developed CM as adults. One study demonstrated no difference
between the wild-type and knock-out mice in the degree of cardiac cell death
as assessed by TUNEL staining
(10). However, in another
study that used a more sensitive PCR-based DNA fragmentation assay increased
DNA fragmentation was reported in the hearts of erbB2-knock-out animals
(9). Recently, Grazette et
al. (11) studied the
effects of erbB2 blockade on cardiomyocyte survival, and showed that erbB2
antibody (erbB2-Ab) caused a loss of mitochondrial membrane potential and an
increase in cell death.The mechanism for the deleterious effects of erbB2 blockade remains
unclear, but a recent report showed that activation of erbB2 reduces
doxorubicin-induced oxidative stress in cardiomyocytes
(12). Therefore, we
hypothesized that erbB2-Ab-induced cell death in cardiomyocytes is a
mitochondrial dependent process that involves ROS production. In this report,
we show that erbB2 levels are decreased in an animal model of myocardial
ischemia and in patients with ischemic CM. We then demonstrate that erbB2
blockade in cardiomyocytes leads to ROS production, and that the antioxidant
N-acetylcysteine (NAC) protects against the damage induced by
erbB2-Ab. We also find that erbB2 signaling in cardiomyocytes occurs through a
mitochondrial, AKT-, and PKCα-dependent pathway. Moreover, the
deleterious effects caused by the loss of erbB2 function require the
pro-apoptotic proteins Bax and Bak. Finally, by using an erbB2-specific siRNA,
we demonstrate that the effects of erbB2 blockade evolve from the specific
inhibition of the erbB2 pathway rather than through nonspecific effects of the
antibody. Together, our results suggest that erbB2 blockade increases ROS
through a mitochondrial pathway. 相似文献
170.
N. Praveen P. M. Naik S. H. Manohar A. Nayeem H. N. Murthy 《Acta Physiologiae Plantarum》2009,31(4):723-728
The major objectives of this study were to investigate an efficient rapid protocol for mass propagation of adventitious shoots
of brahmi using semisolid and liquid cultures; and to assess the amount of bacoside A accumulated in the regenerated shoots.
Leaf explants were grown in vitro on Murashige and Skoog semisolid medium supplemented with 0.5, 1.0, 1.5, 2.0 and 2.5 mg l−1 6-benzyladenine or kinetin (KN) or thidiazuron (TDZ) for 4 weeks. Adventitious shoots developed from leaf explants on all
cytokinin supplemented media. After 4 weeks of incubation, leaf explants were split into two batches and one set was subcultured
on semisolid medium and another set in liquid medium containing same concentration of cytokinins where they have come from.
Highest rate of shoot regeneration was observed for explants cultured on medium with 2 mg l−1 KN. The fresh and dry weight of shoots was also highest with this treatment. Liquid cultures were found suitable for proliferation
of shoots (155.6 shoots per explant) and they also favored highest biomass accumulation (8.60 g fresh and 0.35 g dry biomass).
The bacoside A contents were determined in shoots using HPLC. Analysis revealed that, the contents were highest with shoots
regenerated on medium supplemented with 2 mg l−1 KN. The amount of bacoside A was highest in the shoots regenerated in liquid medium (11.92 mg g−1 DW) and it was 2.2-fold higher compared to shoots grown on semisolid cultures. 相似文献