全文获取类型
收费全文 | 2310篇 |
免费 | 104篇 |
国内免费 | 10篇 |
出版年
2023年 | 25篇 |
2022年 | 61篇 |
2021年 | 133篇 |
2020年 | 50篇 |
2019年 | 91篇 |
2018年 | 78篇 |
2017年 | 58篇 |
2016年 | 98篇 |
2015年 | 110篇 |
2014年 | 137篇 |
2013年 | 186篇 |
2012年 | 193篇 |
2011年 | 169篇 |
2010年 | 70篇 |
2009年 | 94篇 |
2008年 | 101篇 |
2007年 | 109篇 |
2006年 | 98篇 |
2005年 | 101篇 |
2004年 | 64篇 |
2003年 | 69篇 |
2002年 | 49篇 |
2001年 | 24篇 |
2000年 | 16篇 |
1999年 | 12篇 |
1998年 | 11篇 |
1997年 | 11篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 11篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 11篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 11篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1972年 | 10篇 |
1970年 | 6篇 |
1969年 | 4篇 |
1966年 | 3篇 |
排序方式: 共有2424条查询结果,搜索用时 15 毫秒
11.
Khalid Ahmed Peter H. van der Meide John L. Turk 《Cancer immunology, immunotherapy : CII》1989,30(4):213-218
Summary Some conventional and experimental anticancer drugs were tested for their effect on concanavalin-A-induced interferon release from rat splenocytes in vitro. When 2.5 × 106 rat splenocytes/ml, stimulated with 1 µg/ml concanavalin A, were incubated with various non-cytotoxic doses of the vinca alkaloid vincristine, there was an inhibition of the release of interferon in culture supernatants. The antitumour antibiotics bleomycin and Adriamycin, alkylating agents 4-hydroperoxycyclophosphamide and mafosfamide, and the immunoactive peptides FK 156 and FK565 did not affect the release of interferon under similar conditions. However, cyclosporin A, in similar experiments, markedly inhibited the release of interferon . 相似文献
12.
Carl Harald Janson Mahmood Jeddi Tehrani H»kan Mellstedt Hans Wigzell 《Cancer immunology, immunotherapy : CII》1989,28(3):225-232
Summary A murine anti-idiotypic monoclonal antibody (mAb), F1, (IgG2a) was produced against the variable part of the T-cell receptor for antigen (Ti, /) on the tumor cells of a patient with T-cell chronic lymphatic leukemia (CD3+, 8+, 4–). The molecular weight of the protein reactive with mAb F1, comodulation and coprecipitation with anti-CD3 antibody, and the restricted tumor-cell reactivity strongly support the anti-idiotypic nature of mAb F1. MAb F1 also stained 4% of peripheral blood lymphocytes of healthy donors. MAb F1 did not stimulate the tumor cells to DNA synthesis, but stimulated a fraction of the normal peripheral blood lymphocytes, mAb F1 did not mediate antibody-dependent cellular cytotoxicity or complement lysis to any significant degree in vitro. Three infusions of 1–10 mg anti-idiotypic mAb were given over a period of 4 weeks. The plasma half-life for mAb F1 was 3 h in the first 2 h after infusion and 44 h from 2 h to 120 h after infusion. After each treatment a rapid decrease of circulating tumor cells was seen. During the observation period an 80% reduction of the total circulating tumor cells was noted. After the second infusion, IgM and IgG antimouse antibodies were detected. Side-effects from therapy were fever, chills, nausea, vomiting, diarrhea, tachycardia, increase in systolic blood pressure and shortness of breath. Thus, in T-cell malignancies a major reduction of circulating tumor cells can be accomplished by low doses of anti-idiotypic mAb. Anti-idiotypic mAb might be a therapeutic agent of significant importance. 相似文献
13.
14.
Victor D. Ramirez Jianbiao Zheng Khawar M. Siddique 《Cellular and molecular neurobiology》1996,16(2):175-198
Summary 1. There are numerous circumstantial evidence supporting the concept that steroid hormones control cellular function by means other than the nuclear receptor steroid binding mechanism. It is the intent of this report to present evidence indicating that steroids bind to specific sites in neuronal membranes.2. Some of the criteria to define steroid membrane receptors using steroid-BSA conjugates that can be radioiodinated to desired specific activity have been fulfilled for each of the three sex steroids using crude synaptosomal membrane preparations (P2 fractions) from the CNS of female and male rats. Ligand binding for each of the three steroids indicate high-affinity and high-capacity sites with distinct brain selectivity and stereospecificity. For example, 17-E-6-[125I]BSA binds hypothalamic P2 fractions (HYP-P2) with an estimatedK
d of about 3±0.7 nM (X ± SE;n=3), whereas the cerebellum P2 (CB-P2) fractions bind the ligand with aK
d of 34±7 nM and, aB
max of 3 and 42 pmol/mg protein, respectively. Estrogen and testosterone binding fit best a one-single site, while progesterone binding sites can be best represented by a two-binding site, one high-affinity (K
d=1–2 nM) and one low affinity (K
d=62 nM), in CB-P2 fractions from intact adult female rat brain. Kinetics studies for T-3-[125I]BSA indicate that the estimatedK
d of 30±2 nM for the olfactory bulb P2 fractions (OB-P2) from male rats is in good agreement withK
d values computed from Scatchard-derived data using the LIGAND algorithm.3. 17-E-6-[125I]BSA binding sites are stereospecific and appears to be present as early as 5 days of age in both the OB- and the CB-P2 fractions without changes during development. In contrast, P-6-[125I]BSA binding sites are practically absent during days 5 and 12 and appear by day 22.4. Finally, membrane receptor molecules for estrogen and progesterone have been isolated and purified by affinity chromatography and characterized by PAGE and Western blot. Microsequencing of one of the membrane estrogen binding proteins indicates that the high-affinity site corresponds to the OSCP subunit of the proton ATP synthase.5. It remains to be determined if P and T also bind to this complex enzyme or if they bind to other subunits of the family of proton ATPases. Overall the data indicate that steroid hormones conjugated to BSA are important tools to study the reality of membrane steroid receptors. 相似文献
15.
16.
Richard Wales Hazel C. Gorham Khalid Hussain Lynne M. Roberts J. Michael Lord 《Glycoconjugate journal》1994,11(4):274-281
Deleted forms of ricin B chain (RTB) containing only one of the two galactose binding sites were produced inE. coli and targeted to the periplasm by fusion to theompA orompF signal sequences. The proteins were then isolated from the periplasm and their sugar binding properties assessed. Previous studies investigating the properties of such proteins produced inXenopus laevis oocytes suggested that deleted forms of RTB, when not glycosylated, retain their ability to bind simple sugars, unlike the full-length unglycosylated proteins. When produced inE. coli however we found that only one, EB733, of a number of deleted forms of RTB closely related to those previously produced inXenopus laevis oocytes, bound to simple sugars. All of the deletion forms of RTB were found to bind in the asialofetuin binding assay; an assay which has been previously utilized to measure binding of lectins to the terminal galactose residues of glycoprotein oligosaccharides. However, in contrast to glycosylated RTB, binding of the deletion mutants could be competed to only a small degree or not at all with galactose. The only deletion mutant observed to bind to free galactose when produced inE. coli corresponded closely to the complete domain 2 of RTB. It is assumed that this mutant forms a stable structure similar to that of the C-terminal domain in the full-length protein. The structural integrity of EB733 was not only suggested by its sugar binding properties and solubility but also by its consistently higher level of expression and the absence of any apparent susceptibility toE. coli proteases.Abbreviations RTA
ricin toxin A chain
- RTB
ricin toxin B chain
- ER
endoplasmic reticulum
- SDS-PAGE
sodium dodecyl sulphate-polyacrylamide gel electrophoresis
- IPTG
isopropyl -d-thiogalactopyranoside 相似文献
17.
Keisuke Tsutsumi Masami Niwa Naoki Kitagawa Sei-ich Yamaga Takeo Anda †Akihiko Himeno ‡Takaya Sato Humayun Khalid Kohtaro Taniyama Shobu Shibata 《Journal of neurochemistry》1994,63(6):2240-2247
Abstract: We identified and characterized 125I-endothelin-1 (125I-ET-1) binding sites in tumor capillaries isolated from human glioblastomas, using the quantitative receptor autoradiographic technique with pellet sections. Quantification was done using the computerized radioluminographic imaging plate system. High-affinity ET receptors were localized in capillaries from glioblastomas and the surrounding brain tissues (KD = 4.7 ± 1.0 × 10?10 and 1.6 ± 0.3 × 10?10M, respectively; Bmax = 161 ± 38 and 140 ± 37 fmol/mg, respectively; mean ± SEM, n = 5). BQ-123, a selective antagonist for the ETA receptor, potently competed for 125I-ET-1 binding to sections of the microvessels with IC50 values of 5.1 ± 0.3 and 5.1 ± 1.5 nM, and 10?6M BQ-123 displaced 84 and 58% of ET binding to capillaries from tumors and brains, respectively. In addition, competition curves obtained in the presence of increasing concentrations of ET-3 showed two components (IC50 = 5.7 ± 2.5 × 10?10 and 1.4 ± 0.2 × 10?6M for tumor microvessels, 1.8 ± 0.6 × 10?10 and 1.1 ± 0.3 × 10?6M for brain microvessels, respectively). Our results indicate that (a) the method we used is simple and highly sensitive for detecting and characterizing various receptors in tumor capillaries, especially in the case of a sparse specimen, and (b) capillaries in glioblastomas express specific high-affinity ET binding sites, candidates for biologically active ET receptors, which predominantly belong to the ETA subtype. 相似文献
18.
Analysis of γ-Aminobutyric AcidA Receptor Subunits in the Mouse Cochlea by Means of the Polymerase Chain Reaction 总被引:1,自引:0,他引:1
Dennis G. Drescher Glenn E. Green Khalid M. Khan† Kavita Hajela Kirk W. Beisel Barbara J. Morley Anil K. Gupta 《Journal of neurochemistry》1993,61(3):1167-1170
Abstract: Unlike 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces consistent decreases in levels of striatal dopamine (DA) with considerably smaller and more variable effects on mouse brain levels of serotonin (5-HT) and norepinephrine (NE), a novel amine-substituted MPTP analogue, 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2 -MPTP), administered in a standard mouse dosing paradigm for MPTP (20 mg/kg X 4) did not affect striatal DA but led to marked reductions (60–70%) in levels of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), and NE measured in frontal cortex and hippocampus 1 week after treatment. Another 2'-substituted MPTP analogue, 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine, affected cortical and hippocampal 5-HT, 5-HIAA, and NE only minimally, while markedly reducing the DA content in striatum (90%), thus indicating that the substituent (-NH2 versus -CH3 ) at the 2'position is important for the differential effects of these MPTP analogues. In a replication study with a 3-week end point, hippocampal and cortical 5-HT, 5-HIAA, and NE levels remained depressed with no indication of recovery. These results suggest that 2'-NH2 -MPTP may be a novel, regionally selective neurotoxin for serotonergic and norad-renergic nerve terminals. 相似文献
19.
Khalid Meksem Dario Leister Johan Peleman Marc Zabeau Francesco Salamini Christiane Gebhardt 《Molecular & general genetics : MGG》1995,249(1):74-81
The R1 allele confers on potato a race-specific resistance to Phytophthora infestans. The corresponding genetic locus maps on chromosome V in a region in which several other resistance genes are also located. As part of a strategy for cloning R1, a high-resolution genetic map was constructed for the segment of chromosome V that is bordered by the RFLP loci GP21 and GP179 and includes the R1 locus. Bulked segregant analysis and markers based on amplified fragment length polymorphisms (AFLP markers) were used to select molecular markers closely linked to R1. Twenty-nine of approximately 3200 informative AFLP loci displayed linkage to the R1 locus. Based on the genotypic analysis of 461 gametes, eight loci mapped within the GP21–GP179 interval. Two of those could not be seperated from R1 by recombination. For genotyping large numbers of plants with respect to the flanking markers GP21 and GP179 PCR based assays were also developed which allowed marker-assisted selection of plants with genotypes Rr and rr and of recombinant plants. 相似文献
20.
Mahmood Vahedian Liang Shi Tong Zhu Ronald Okimoto Kathleen Danna Paul Keim 《Plant molecular biology》1995,29(4):857-862
Repetitive DNA sequences comprise a large percentage of plant genomes, and their characterization provides information about both species and genome evolution. We have isolated a recombinant clone containing a highly repeated DNA element (SB92) that is homologous to ca. 0.9% of the soybean genome or about 105 copies. This repeated sequence is tandemly arranged and is found in four or five major genomic locations. FISH analysis of metaphase chromosomes suggests that two of these locations are centromeric. We have determined the sequence of two cloned repeats and performed genomic sequencing to obtain a consensus sequence. The consensus repeat size was 92 bp and exhibited an average of 10% nucleotide substitution relative to the two cloned repeats. This high level of sequence diversity suggests an ancient origin but is inconsistent with the limited phylogenetic distribution of SB92, which is found an high copy number only in the annual soybeans. It therefore seems likely that this sequence is undergoing very rapid evolution. 相似文献