全文获取类型
收费全文 | 4826篇 |
免费 | 406篇 |
国内免费 | 396篇 |
专业分类
5628篇 |
出版年
2024年 | 25篇 |
2023年 | 151篇 |
2022年 | 222篇 |
2021年 | 261篇 |
2020年 | 254篇 |
2019年 | 321篇 |
2018年 | 288篇 |
2017年 | 216篇 |
2016年 | 261篇 |
2015年 | 282篇 |
2014年 | 352篇 |
2013年 | 513篇 |
2012年 | 186篇 |
2011年 | 224篇 |
2010年 | 160篇 |
2009年 | 191篇 |
2008年 | 200篇 |
2007年 | 203篇 |
2006年 | 186篇 |
2005年 | 147篇 |
2004年 | 140篇 |
2003年 | 122篇 |
2002年 | 122篇 |
2001年 | 78篇 |
2000年 | 41篇 |
1999年 | 63篇 |
1998年 | 64篇 |
1997年 | 41篇 |
1996年 | 38篇 |
1995年 | 37篇 |
1994年 | 35篇 |
1993年 | 32篇 |
1992年 | 14篇 |
1991年 | 22篇 |
1990年 | 12篇 |
1989年 | 16篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 14篇 |
1985年 | 12篇 |
1984年 | 22篇 |
1983年 | 11篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1976年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有5628条查询结果,搜索用时 15 毫秒
11.
B. Seshadri Sekhar C. K. Ramakrishna Kurup T. Ramasarma 《Molecular and cellular biochemistry》1990,95(1):61-70
A membrane protein recognized by monoclonal antibody SQM1 was identified in human squamous carcinomas, including those originating in the head and neck (SqCHN), lung and cervix. Cell lines derived from SqCHN of previously untreated patients expressed high amounts of this protein. In contrast, many cell lines established from SqCHN of patients previously treated with chemotherapy and/or radiation showed diminished amounts of this SQM1 protein. The expression of SQM1 antigen was determined in several SgCHN cell lines made resistant by exposure to methotrexate (MTX) in vitro. The parent cell lines all exhibited strong binding to SQM1 antibody. The MTX-resistant sublines showed much lower membrane binding of SQM1. The lowest SQM1 reactivity was found in cell lines with high resistance to MTX and with diminished rate of MTX transport. Some highly MTX-resistant cell lines which had high levels of dihydrofolate reductase, but which retained a high rate of MTX transport, also retained high levels of SQM1 binding. Reduced SQM1 protein was also found in SgCHN cells which developed resistance to the alkylating drug cis-platinum (CDDP) and which showed reduced membrane transport of CDDP. Cell growth kinetics and non-specific antigenic shifts were not responsible for the differences in SQM1 binding between the parent cell lines and their drug-resistant sublines. The finding of a novel protein which is reduced in cells resistant to MTX and CDDP could contribute to our understanding of the basic mechanisms of drug resistance. By detecting SQM1 protein in clinical specimens, it may be possible to monitor the development of drug resistance in tumors.Abbreviations SqCHN
Squamous Carcinoma of the Head and Neck
- MTX
Methotrexate
- CDDP
Cis-Platinum
- DHFR
Dihydrofolate Reductase 相似文献
12.
A simple procedure is described for the determination of the photosensitizing potency of drugs, using three leukemic cell lines, two of lymphocytic origin, L1210 and P388 and one of erythroid type, Friend-745. The procedure allows one to investigate several aspects of the photosensitization properties of tested compounds such as cellular localization and direct (trypan blue exclusion) or delayed (clonogenicity) photomediated toxicities.The method was assessed using crude hematoporphyrin derivative (HPD) as well as dihematoporphyrin ether (DHE) or commercially available Photofrin II. Results were compared to those obtained with normal cells, e.g spleen lymphocytes and erythropoietic stem cells (CFU-e), and discussed in the light of the relative response of normal versus transformed cells.Abbreviations DHE
Dihematoporphyrin Ether
- FCS
Fetal Calf Serum
- HPD
Hematoporphyrin Derivative
- PDT
Photodynamic Therapy 相似文献
13.
Lawrence D. Mayer Marcel B. Bally Michael J. Hope Pieter R. Cullis 《Chemistry and physics of lipids》1986,40(2-4):333-345
As a prerequisite for the use of liposomes for delivery of biologically active agents, techniques are required for the efficient and rapid entrapment of such agents in liposomes. Here we review the variety of procedures available for trapping hydrophilic and hydrophobic compounds. Considerations which are addressed include factors influencing the choice of a particular liposomal system and techniques for the passive entrapment of drugs in multilamellar vesicles and unilamellar vesicles. Attention is also paid to active trapping procedures relying on the presence of (negatively) charged lipid or transmembrane ion gradients. Such gradients are particularly useful for concentrating lipophilic cationic drugs inside liposomes, allowing trapping efficiencies approaching 100%. 相似文献
14.
藏马鸡(Crossoptilon crossoptilon)的繁殖生态研究 总被引:2,自引:0,他引:2
藏马鸡是典型高山地牺雉类,见于海拔3,500—3,900米的针叶林带。自4月中至7月底为繁殖期。一“夫”配一“妻”。营巢于海拔3,544—3,790米的岩洞、灌丛中或倒木下。共发现4巢,3巢已被破坏,成功率25%。近年来,由于过渡砍伐森林,天敌的伤害,自身弱点(繁殖率低,成熟期长(3年左右)以及其他因素,藏马鸡的数量日趋减少,正面临绝种的厄运。必须及时地采取有效保护措施。 相似文献
15.
Human blood was sheared between rotating polyethylene disks and plasma hemoglobin measured at intervals to produce kinetic
hemolysis curves (KHC), plotted as free hemoglobin concentration vs time. The KHC produced by blood samples incubated in the
presence of penicillin, streptomycin, gentamicin, and amikacin lie always below those for control samples, indicating a reduction
in hemolysis; this reduction was greater as the drug concentration was increased. Explanations in terms of alterations in
red cell structure were sought by several characterization tests of amikacin-loaded blood samples. Drug-localization studies
demonstrated that significant fractions of the total dosage were associated with the red-cell membrane. Resistive pulse spectroscopy
was used to show how amikacin affected cell size, deformability, and osmotic fragility; results were sensitive to storage
age of the blood. In all cases, the effect of shearing was to reduce cell size, deformability, and osmotic fragility. Mechanisms
for hemolytic protection by drugs are proposed. 相似文献
16.
Dr. Dimitrij A. Kuznetsov Nikolay V. Zavijalov Gennadij J. Kelman Alexander V. Govorkov 《Cell biology and toxicology》1986,2(3):337-340
A variety of methylated 4-oxypiperidine derivatives were tested for their ability to inhibit protein synthesis in vitro. A direct correlation was found between the extent of methylation of these compounds and their inhibitory activity in a rabbit reticulocyte lysate cell-free translation system.Abbreviation IC50
50% inhibitory concentration 相似文献
17.
Venkataraman Amarnath Traci L. Miller Arthur D. Broom 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1983,741(2):224-229
Poly(5-fluoro-2′-deoxyuridylic acid) was synthesized and its properties were compared with those of poly(dT) and poly(dU). It readily complexed with poly(dA). The 1:1 complex melted at about 20°C lower than poly(dA) · poly(dT). A triple-stranded helix, poly(dA)·2 poly(dF5U) was formed only in high salt (2.0 M NaCl). 相似文献
18.
Study of the in vitro bioactivation of albendazole in human liver microsomes and hepatoma cell lines
Sylvie Rolin Hajar Souhaili-El Amri Anne-Marie Batt Michele Levy Denyse Bagrel Gerard Siest 《Cell biology and toxicology》1989,5(1):1-14
The metabolism of albendazole (ABZ), a benzimidazole anthelminthic, was studied in either microsomal preparations of human liver biopsies or cultured human hepatoma cell lines. Metabolites were analyzed by HPLC. Our data show that microsomes from human biopsies and two human cell lines, HepG2 and Hep3B, oxidize the drug to the sulfoxide very efficiently, whereas the third cell line tested, SK-HEP-1, does not. Both cytochrome P-450 dependent monooxygenases and favin-containing monooxygenases appear to be involved in human ABZ metabolism. Using the cell line displaying the highest ABZ-metabolizing activity, HepG2, the cytotoxic and the inducing effects of the parent drug ABZ and of two primary metabolites, the sulfoxide and the sulfone were studied. These three chemicals provoked a rise in mitotic index resulting from cell division blockage at the prophase or at the metaphase (ABZ metabolites) stage, and ABZ was more cytotoxic than its metabolites. With regard to enzyme-inducing effects, our data clearly demonstrate that the sulfoxide and, to a lesser degree, the sulfone are potent inducers of some drug metabolizing enzymes (i.e., cytochrome P-488 dependent monooxygenases and UDP glucuronyltransferase), whereas ABZ fails to increase and even slightly decreases these enzymatic activities. In conclusion, the HepG2 human hepatoma cell line appears to be suitable for the study of many parameters of metabolism and action of ABZ and other structurally related compounds in humans.Abbreviations ABZ
albendazole
- B[a]P
benzo[a]pyrene
- HPLC
high-performance liquid chromatography
- MC
3-methylcholanthrene
- MFO
mixed-function oxidase
- UDPGT
UDP-glucuronyltransferase 相似文献
19.
青海藏族青少年骨龄与生长发育关系研究 总被引:1,自引:0,他引:1
本文报告了青海省境内,世居在海拔3000-4000米地区的728名7-18岁健康藏族青少年学生的手、腕部骨骼发育情况,对骨化中心出现和骨骺愈合求出了50%出现年龄,并对骨龄与青春期身高突增的关系及与月经初衬潮的关系进行了分析。 相似文献
20.
Using data for 27 Texas counties from 1978-1987, it is shown that the incidence rates of suicide, homicide, and rape are significantly higher in counties whose drinking water supplies contain little or no lithium than in counties with water lithium levels ranging from 70-170 micrograms/L; the differences remain statistically significant (p less than 0.01) after corrections for population density. The corresponding associations with the incidence rates of robbery, burglary, and theft were statistically significant with p less than 0.05. These results suggest that lithium has moderating effects on suicidal and violent criminal behavior at levels that may be encountered in municipal water supplies. Comparisons of drinking water lithium levels, in the respective Texas counties, with the incidences of arrests for possession of opium, cocaine, and their derivatives (morphine, heroin, and codeine) from 1981-1986 also produced statistically significant inverse associations, whereas no significant or consistent associations were observed with the reported arrest rates for possession of marijuana, driving under the influence of alcohol, and drunkenness. These results suggest that lithium at low dosage levels has a generally beneficial effect on human behavior, which may be associated with the functions of lithium as a nutritionally-essential trace element. Subject to confirmation by controlled experiments with high-risk populations, increasing the human lithium intakes by supplementation, or the lithiation of drinking water is suggested as a possible means of crime, suicide, and drug-dependency reduction at the individual and community level. 相似文献