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1.
Minh C. Nguyen Guang Huan Tu Kathryn E. Koprivnikar Melissa Gonzalez-Edick Karin U. Jooss Thomas C. Harding 《Cancer immunology, immunotherapy : CII》2010,59(9):1313-1323
A critical factor in clinical development of cancer immunotherapies is the identification of tumor-associated antigens that
may be related to immunotherapy potency. In this study, protein microarrays containing >8,000 human proteins were screened
with serum from prostate cancer patients (N = 13) before and after treatment with a granulocyte–macrophage colony-stimulating factor (GM-CSF)-secreting whole cell immunotherapy.
Thirty-three proteins were identified that displayed significantly elevated (P ≤ 0.05) signals in post-treatment samples, including three proteins that have previously been associated with prostate carcinogenesis,
galectin-8, T-cell alternative reading frame protein (TARP) and TNF-receptor-associated protein 1 (TRAP1). Expanded analysis
of antibody induction in metastatic, castration-resistant prostate cancer (mCRPC) patients (N = 92) from two phase 1/2 trials of prostate cancer immunotherapy, G-9803 and G-0010, indicated a significant (P = 0.03) association of TARP antibody induction and median survival time (MST). Antibody induction to TARP was also significantly
correlated (P = 0.036) with an increase in prostate-specific antigen doubling time (PSADT) in patients with a biochemical (PSA) recurrence
following prostatectomy or radiation therapy (N = 19) from in a previous phase 1/2 trial of prostate cancer immunotherapy, G-9802. RNA and protein encoding TARP and TRAP1
was up-regulated in prostate cancer tissue compared to matched normal controls. These preliminary findings suggest that antibody
induction to TARP may represent a possible biomarker for treatment response to GM-CSF secreting cellular immunotherapy in
prostate cancer patients and demonstrates the utility of using protein microarrays for the high-throughput screening of patient-derived
antibody responses. 相似文献
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Melissa D. Lage Adrianne M. C. Pittman Alessandro Roncador Barbara Cellini Chandra L. Tucker 《PloS one》2014,9(4)
Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele. 相似文献
6.
Shrishailam Yemul Carole Berger Melissa Katz Alison Estabrook Richard Edelson Hagan Bayley 《Cancer immunology, immunotherapy : CII》1990,30(6):317-322
Summary Molecules such as antibodies that bind to cell surfaces can be used to deliver cytotoxic drugs to selected cells. To be effective the drug must usually be taken into the cells by endocytosis. In this study a T-cell line (CCRFCEM) was effectively killed by liposomes carrying a photosensitizer and bearing the antibody OKT4 (anti-CD4). The unconjugated antibody does not induce antigenic modulation in the target cells, an indication of the absence of endocytosis, and would therefore not normally have been selected as an agent for drug delivery. It cannot, however, be concluded with certainty that the conjugates act at the cell surface and several alternative explanations of their efficacy are offered. 相似文献
7.
Evidence Against the Involvement of Ionically Bound Cell Wall Proteins in Pea Epicotyl Growth 总被引:1,自引:1,他引:0
Ionically bound cell wall proteins were extracted from 7 day old etiolated pea (Pisum sativum L. cv Alaska) epicotyls with 3 molar LiCl. Polyclonal antiserum was raised in rabbits against the cell wall proteins. Growth assays showed that treatment of growing region segments (5-7 millimeters) of peas with either dialyzed serum, serum globulin fraction, affinity purified immunoglobulin, or papain-cleaved antibody fragments had no effect on growth. Immunofluorescence microscopy confirmed antibody binding to cell walls and penetration of the antibodies into the tissues. Western blot analysis, immunoassay results, and affinity chromatography utilizing Sepharose-bound antibodies confirmed recognition of the protein preparation by the antibodies. Experiments employing in vitro extension as a screening measure indicated no effect upon extension by antibodies, by 50 millimolar LiCl perfusion of the apoplast or by 3 molar LiCl extraction. Addition of cell wall protein to protease pretreated segments did not restore extension nor did addition of cell wall protein to untreated segments increase extension. It is concluded that, although evidence suggests that protein is responsible for the process of extension, the class(es) of proteins which are extracted from pea cell walls with 3 molar LiCl are probably not involved in this process. 相似文献
8.
Alternatively spliced RNAs encode several isoforms of CD46 (MCP), a regulator of complement activation 总被引:2,自引:0,他引:2
Damian F. J. Purcell Sarah M. Russell Nicholas J. Deacon Melissa A. Brown David J. Hooker Ian F. C. McKenzie 《Immunogenetics》1991,33(5-6):335-344
Five alternative cDNA clones were isolated for CD46, also known as the membrane cofactor protein (MCP) for the factor I-mediated cleavage of the complement convertases. One of these cDNA clones (a) was identical to an earlier MCP clone. The other four CD46 clones 3ontained the four NH2-terminanl short consensus repeat (SCR) units of MCP, but differed at the region encoding the carboxyl-terminal of the protein which includes an extracellular segment rich in Ser, Thr, and Pro residues, a hydrophobic membrane-spanning domain, and a 33 amino acid cytoplasmic tail. The different CD46 cDNAs have variously: (b) inserted a 93 base pair (bp) exon resulting in a new cytoplasmic tail of 26 amino acids; (c) deleted a 42 bp exon from the extracellular Ser/Thr rich region; (d) used a cryptic splice acceptor sequence to delete 37 bp from an exon encoding transmembrane sequence; or (e) failed to splice the intron after the four SCR units. These were shown by northern blot and polymerase chain reaction to arise by alternative splicing of CD46 RNA. Forms (a), (b), and (c) of CD46 RNA are common in placental RNA, but (d) was rare, and (e) was incompletely processed and therefore aberrant. The polymerase chain reaction (PCR) was used to map the sites of the intron/exon junctions and demonstrate further possible splice variants of CD46. The alternative RNAs for CD46 may correlate to the different isoforms of CD46 found in different tissues, tumors, and in serum.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number M58050.
Address correspondence and offprint requests to: D. F. J. Purcell. 相似文献
9.
Joseph R. Songer 《Applied microbiology》1967,15(1):35-42
A system for studying the effects of relative humidity (RH) and temperature on biological aerosols, utilizing a modified toroid for a static aerosol chamber, is described. Studies were conducted at 23 C and at three RH levels (10, 35, and 90%) with four viruses (Newcastle disease virus, infectious bovine rhinotracheitis virus, vesicular stomatitis virus, and Escherichia coli B T3 bacteriophage). Virus loss on aerosol generation was consistently lower at 90% than at 10 or 35% RH. When stored at 23 C, Newcastle disease virus and vesicular stomatitis virus survived best at 10% RH. Infectious bovine rhinotracheitis virus and E. coli B T3 bacteriophage survived storage at 23 C best at 90% RH. 相似文献
10.
Role of Differential Air Pressure Zones in the Control of Aerosols in a Large Animal Isolation Facility 总被引:1,自引:1,他引:0 下载免费PDF全文
The uncontrolled transmission of hog cholera in a large animal isolation facility, designed to control the movement of aerosols within and between individual wings of a multiunit building, indicated the need for a critical study of aerosol behavior under existing conditions of operation. Studies with aerosols of Escherichia coli B T3 bacteriophage (T3 coliphage) conclusively demonstrated the impossibility of obtaining the desired control by means of a "static" air balance relationship between adjacent areas within the facility. Modifications needed to provide the desired control of the air-handling system are outlined and discussed. 相似文献