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951.
To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging, the over-expression of B cells in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system) was investigated. In the current investigation, we present the labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+) precursor for radioimmunoimaging (RII) of the tumor prior to its treatment with (90)Y labeled IBTN. Labeled IBTN was radiobiologically characterized in terms of radiochemical purity, in vitro stability in human plasma, immunoreactivity, binding with Raji and Ramos cells and biodistribution in a female nude mouse (FNM) model. It was observed that the reduced IBTN (rIBTN) showed more promising radiobiologic characteristics than the nonreduced IBTN. Significantly higher transchelation was seen in excess cysteine compared with histidine. The radioconjugate showed higher saturated binding affinity with CD20 antigen. Significantly higher target (tumor) to background ratios were observed 1 h post-injection (p.i.). Based on radiochemical purity, in vitro stability, immunoreactivity, binding and biodistrubtion in the FNM model, we recommend the radiolabeling of the rIBTN using tricarbonyl technique as a potential RII agent. 相似文献
952.
Using first principle calculations, we investigated cation-π interactions between alkali cations (Li(+), Na(+), and K(+)) and pristine C(24) or doped fullerenes of BC(23), and NC(23). The most suitable adsorption site is found to be atop the center of a six-membered ring of the exterior surface of C(24) molecule. Interaction energies of these cations decreased in the order: Li(+)?>?Na(+)?>?K(+), with values of -31.82, -22.36, and -15.68 kcal mol(-1), respectively. It was shown that the interaction energies are increased and decreased by impurity doping of B and N atoms in adjacent wall of adsorption site, depending on electron donating or receptivity of the doping atoms. 相似文献
953.
954.
Phage display is a powerful technology that enables the discovery of peptide ligands for many targets. Chemical modification of phage libraries have allowed the identification of ligands with properties not encountered in natural polypeptides. In this report, we demonstrated the synthesis of 2 × 10(8) genetically encoded glycopeptides from a commercially available phage-displayed peptide library (Ph.D.-7) in a two-step, one-pot reaction in <1.5 h. Unlike previous reports, we bypassed genetic engineering of phage. The glycan moiety was introduced via an oxime ligation following oxidation of an N-terminal Ser/Thr; these residues are present in the peptide libraries at 20-30% abundance. The construction of libraries was facilitated by simple characterization, which directly assessed the yield and regioselectivity of chemical reactions performed on phage. This quantification method also allowed facile yield determination of reactions in 10(9) distinct molecules. We envision that the methodology described herein will find broad application in the synthesis of custom chemically modified phage libraries. 相似文献
955.
Mariana Brait Myriam Loyo Eli Rosenbaum Kimberly L. Ostrow Alina Markova Silvana Papagerakis Marianna Zahurak Steven M. Goodman Martha Zeiger David Sidransky Christopher B. Umbricht Mohammad O. Hoque 《Epigenetics》2012,7(7):710-719
Our aim was to comprehensively analyze promoter hypermethylation of a panel of novel and known methylation markers for thyroid neoplasms and to establish their relationship with BRAF mutation and clinicopathologic parameters of thyroid cancer. A cohort of thyroid tumors, consisting of 44 cancers and 44 benign thyroid lesions, as well as 15 samples of adjacent normal thyroid tissue, was evaluated for BRAF mutation and promoter hypermethylation. Genes for quantitative methylation specific PCR (QMSP) were selected by a candidate gene approach. Twenty-two genes were tested: TSHR, RASSF1A, RARβ2, DAPK, hMLH1, ATM, S100, p16, CTNNB1, GSTP1, CALCA, TIMP3, TGFßR2, THBS1, MINT1, CTNNB1, MT1G, PAK3, NISCH, DCC, AIM1 and KIF1A. The PCR-based “mutector assay” was used to detect BRAF mutation. All p values reported are two sided. Considerable overlap was seen in the methylation markers among the different tissue groups. Significantly higher methylation frequency and level were observed for KIF1A and RARß2 in cancer samples compared with benign tumors. A negative correlation between BRAF mutation and RASSF1A methylation, and a positive correlation with RARß2 methylation were observed in accordance with previous results. In addition, positive correlation with TIMP3 and a marginal correlation with DCC methylation were observed. The present study constitutes a comprehensive promoter methylation profile of thyroid neoplasia and shows that results must be analyzed in a tissue-specific manner to identify clinically useful methylation markers. Integration of genetic and epigenetic changes in thyroid cancer will help identify relevant biologic pathways that drive its development. 相似文献
956.
Lithium preparations are commonly used drug in treating mental disorders and bipolar diseases, but metal's cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of lithium in freshly isolated rat hepatocytes. Lithium cytotoxicity were associated with reactive oxygen species (ROS) formation and collapse of mitochondrial membrane potential and cytochrome c release into the hepatocyte cytosol. All of the mentioned lithium-induced cytotoxicity markers were significantly (P?0.05) prevented by ROS scavengers, antioxidants, mitochondrial permeability transition pore sealing agents and adenosine triphosphate generators. Hepatocyte glutathione (GSH) was also rapidly oxidized and GSH-depleted hepatocytes were more resistant to lithium-induced oxidative stress markers. This suggests that lithium is activated by GSH. Our results also showed that CYP2E1 is involved in lithium oxidative stress mechanism. Lithium cytotoxicity was also associated with mitochondrial injuries initiated by increased ROS formation resulted from metal-CYP2E1 destructive interaction or metal-induced disruption of mitochondrial electron transfer chain. Methyl donors such as betaine, methionine, or folic acid prevented lithium cytotoxicity, and this suggests that this metal is detoxified by phase II metabolic methylation. In conclusion lithium-induced cytotoxicity could be attributed to oxidative stress and mitochondrial dysfunction. 相似文献
957.
958.
Rajkumari Sanjukta Mohammad Samir Farooqi Naveen Sharma Anil Rai Dwijesh Chandra Mishra Dhananjaya P Singh 《Bioinformation》2012,8(22):1087-1095
Chromohalobacter salexigens, a Gammaproteobacterium belonging to the family Halomonadaceae, shows a broad salinity range for
growth. In order to reveal the factors influencing architecture of protein coding genes in C. salexigens, pattern of synonymous codon
usage bias has been investigated. Overall codon usage analysis of the microorganism revealed that C and G ending codons are
predominantly used in all the genes which are indicative of mutational bias. Multivariate statistical analysis showed that the genes
are separated along the first major explanatory axis according to their expression levels and their genomic GC content at the
synonymous third positions of the codons. Both NC plot and correspondence analysis on Relative Synonymous Codon Usage
(RSCU) indicates that the variation in codon usage among the genes may be due to mutational bias at the DNA level and natural
selection acting at the level of mRNA translation. Gene length and the hydrophobicity of the encoded protein also influence the
codon usage variation of genes to some extent. A comparison of the relative synonymous codon usage between 10% each of highly
and lowly expressed genes determines 23 optimal codons, which are statistically over represented in the former group of genes and
may provide useful information for salt-stressed gene prediction and gene-transformation. Furthermore, genes for regulatory
functions; mobile and extrachromosomal element functions; and cell envelope are observed to be highly expressed. The study
could provide insight into the gene expression response of halophilic bacteria and facilitate establishment of effective strategies to
develop salt-tolerant crops of agronomic value. 相似文献
959.
About 1700 years BC, the prophet Zoroaster declared equal right for women and men to choose their "own ways." There is much evidence that ancient Persians believed in the equal contribution of women and men toward producing a child, and all its hereditary characteristics.Even more surprising are the phrases in Vandidad book, which were gathered by Mobedans in the Mad dynasty about egg extraction (gametes) from animal reproductive organs (gonads) and their storage for future conception.Centuries later, Western philosopher beliefs in regard to reproduction were contrary to Persian knowledge. The Greek philosophers believed that man's water (semen) contains all human characteristics, and the female uterus is only responsible for nurturing and development of fetus. After detection of the ovum (de Graaf 2(nd) half 17 century) Malpigy proposed the preformation theory (ovist) which means there is a miniature human inside ovum, that grows after Semen has entered the uterus and grow into a well-developed fetus. This hypothesis was later delegated to spermatozoa. These contradictory and inappropriate beliefs were subject to discussions and dispute, until C.E. Wolf demonstrated that the embryo is a product of the fertilization of ovum by spermatozoa.800 years prior this the sage Ferdowsi "The Great Iranian Poet" explains nicely the equal participation of man and woman in the production of the fetus and transmission of characters.After the renaissance and especially in recent years, tremendous achievements have been made in unraveling biological secrets of reproduction. There was no work o n genetics in Iran until 1936, when a genetic course was added to the biology curriculum in related colleges and universities; Iranian Genetics Society was founded in 1966, initiating a steady movement in this field.Although there was an inevitable gap during the revolution and war in our country, now there is great effort by researchers to eliminate the gap and bring us into the mainstream of world science, and development in biomedical sciences in the third millennium. 相似文献
960.
Santosh Kumar Ramachandra Jadhav Krunal Arvind Patel Bhushan Bhalchandra Dholakia Bashir Mohammad Khan 《Bioinformation》2012,8(19):943-949
Medicinal plants are extensively utilized in traditional and herbal medicines, both in India and around the world due to the
presence of diverse low molecular weight natural products such as flavonoids, alkaloids, terpenoids and sterols. Flavonoids which
have health benefits for humans are the large class of phenylpropanoid-derived secondary metabolites and are mostly glycosylated
by UDP-glycosyltransferases (UGTs). Although large numbers of different UGTs are known from higher plants, very few protein
structures have been reported till now. In the present study, the three-dimensional model of flavonoid specific glycosyltransferases
(WsFGT) from Withania somnifera was constructed based on the crystal structure of plant UGTs. The resulted model was assessed
by various tools and the final refined model revealed GT-B type fold. Further, to understand the sugar donors and acceptors
interactions with the active site of WsFGT, docking studies were performed. The amino acids from conserved PSPG box were
interacted with sugar donor while His18, Asp110, Trp352 and Asn353 were important for catalytic function. This structural and
docking information will be useful to understand the glycosylation mechanism of flavonoid glucosides.