全文获取类型
收费全文 | 6680篇 |
免费 | 557篇 |
国内免费 | 356篇 |
出版年
2024年 | 23篇 |
2023年 | 188篇 |
2022年 | 257篇 |
2021年 | 327篇 |
2020年 | 300篇 |
2019年 | 406篇 |
2018年 | 336篇 |
2017年 | 255篇 |
2016年 | 321篇 |
2015年 | 333篇 |
2014年 | 436篇 |
2013年 | 652篇 |
2012年 | 245篇 |
2011年 | 297篇 |
2010年 | 207篇 |
2009年 | 269篇 |
2008年 | 286篇 |
2007年 | 306篇 |
2006年 | 254篇 |
2005年 | 222篇 |
2004年 | 213篇 |
2003年 | 154篇 |
2002年 | 163篇 |
2001年 | 124篇 |
2000年 | 94篇 |
1999年 | 102篇 |
1998年 | 111篇 |
1997年 | 72篇 |
1996年 | 60篇 |
1995年 | 63篇 |
1994年 | 57篇 |
1993年 | 52篇 |
1992年 | 34篇 |
1991年 | 48篇 |
1990年 | 27篇 |
1989年 | 35篇 |
1988年 | 19篇 |
1987年 | 29篇 |
1986年 | 24篇 |
1985年 | 23篇 |
1984年 | 31篇 |
1983年 | 21篇 |
1982年 | 19篇 |
1981年 | 18篇 |
1980年 | 19篇 |
1979年 | 19篇 |
1978年 | 12篇 |
1977年 | 5篇 |
1976年 | 7篇 |
1973年 | 7篇 |
排序方式: 共有7593条查询结果,搜索用时 15 毫秒
21.
The purine path to chemotherapy 总被引:4,自引:0,他引:4
Gertrude B. Elion 《Bioscience reports》1989,9(5):509-529
Antimetabolites of purine metabolism have found a use as anti-leukaemic, antiprotozoal and antiviral drugs, in immunosuppression and transplantation, and in gout and hyperuricemia. Their mechanisms of action are reviewed.Nobel Lecture given on December 8, 1988; by Dr Gertrude B. Elion and published inLes Prix Nobel 1988, printed in Sweden by Norstedts Tryckeri, Stockholm, Sweden, 1989, republished here with the permission of the Nobel Foundation, the copyright holder. 相似文献
22.
Francis A. Drobniewski 《Bioscience reports》1989,9(2):139-156
Immunotoxins consist of monoclonal or polyclonal antibodies conjugated to bacterial or plant toxins. The toxins used are typically of the A-B type in which a toxic A chain is coupled to a B chain responsible for cell binding and facilitation of A chain entry into the cytosol. Two broad strategies have been followed: coupling intact toxins, or A chains alone, to antibodies. This review examines current progress inin vitro andin vivo research, including recent clinical studies, concentrating principally on ricin or ricin A chain conjugates. The future role of conjugates using membrane-acting toxins, immunolysins, is also discussed. 相似文献
23.
A single intraperitoneal injection of DL-methionine (500 mg/kg body wt.) to adult male Wistar rats was shown to significantly
induce all the components of the hepatic microsomal mixed function oxidase system such as NADPH cytochrome C reductase activity,
cytochromes P-450 and b5, as well as activities of drug metabolizing enzymes such as aminopyrine demethylase and uridine 5′ -diphosphate-glucuronosyltransferase.
Combined administration of nicotinamide (250 mg/kg body wt.) and DL-methionine (500 mg/kg body wt.) was shown to bring about
an additional increase (25-30%) in the activities of these enzymes as compared to their induction on independent administration
of the two endobiotics. In rats bearing Yoshida sarcoma (ascites) tumour as well as in normal rats injected with serum from
tumour bearing animals, the decreased activities of hepatic mixed function oxidases could be restored to their normal levels
by administration of DL-methionine (500 mg/kg body wt.) to these rats. Whereas actinomycin D (1 mg/kg body wt.) had no effect
on the increased incorporation of [14C] labelled leucine into microsomal proteins following administration of nicotinamide, the enhanced incorporation of the label
following DL-methionine administration was completely inhibited by the same dose of actinomycin D. Administration of cycloheximide
(0·5 mg/kg body wt.) to rats could completely inhibit the increased incorporation of [14C] leucine into hepatic microsomal proteins following independent administration of nicotinamide and DL-methionine. Similar
inhibitory pattern with actinomycin D and cycloheximide was also demonstrated in case of induction of NADPH cytochromeC reductase activity by both these endobiotics. 相似文献
24.
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
25.
In this note we outline some recent results on the development of a statistical testing methodology for inverse problems involving partial differential equation models. Applications to several problems from biology are presented. The statistical tests, which are in the spirit of analysis of variance (ANOVA), are based on asymptotic distributional results for estimators and residuals in a least squares approach.Research supported in part under grants NSF MCS 8504316, NASA NAG-1-517, and AFOSRF-49620-86-C-0111. Part of this research was carried out while the first author was a visiting scientist at the Institute for Computer Applications in Science and Engineering (ICASE), NASA Langley Research Center, Hampton, VA, which is operated under NASA contracts NASI-18107 and NASI-18605 相似文献
26.
Midori Hiramatsu Rei Edamatsu Shigeo Suzuki Masakazu Shimada Akitane Mori 《Neurochemical research》1990,15(8):821-825
Inbred mutant El mice are highly susceptible to convulsive seizures upon tossing stimulation. The levels of excitatory (e.g. glutamate and aspartate) and inhibitory amino acids [e.g. -aminobutyrate (GABA)] were examined in discrete regions of stimulated El mice [El(+)] non-stimulated El mice [El(-)] and ddY mice, which do not have convulsive disposition. In comparison with ddY, a general increased levels of aspartate, glutamate, glutamine, and taurine were detected in brain regions of El(-). The levels of GABA and glycine were almost the same in ddY and El(-). Compared to El(+), the levels of aspartate, glutamate, glutamine, and GABA in El(-) were either the same or higher. In the case of taurine and glycine, the levels in El(-) were either the same or lower than El(+). Alanine is special in that El(-) have a higher level than El(+) in hippocampus but lower in cerebellum. Furthermore, while marked changes were registered in several brain regions, none of the amino acids investigated showed any significant differences in the hypothalamus of three different groups of mice. 相似文献
27.
A. G. M. Steerneman E. A. van der Meulen W. Schaafsma G. N. van Vark 《Human Evolution》1990,5(5):449-456
Research on human evolution and sexual dimorphism motivates an interesting test problem. In studying hominid phylogeny it
is of interest to test whether parallel evolution plays a role. With regard to sexual dimorphism it is of interest to known
whether the directions of sexual dimorphism in the populations being compared are the same. We show that testing these two
problems gives rise to the same type of hypothesis testing, viz. the problem of testing the hypothesis that the means of independent,
normally distributed random vectors with unit covariance matrices are situated on a straight line through the origin. A test
is proposed and applied to study the sexual dimorphism of 20 recent skull populations. In this example the hypothesis of equal
directions of sexual dimorphism is rejected. The classical theory of constructing multiple discriminant functions (canonical
variates) is adapted to the problem of comparing sexual dimorphisms. 相似文献
28.
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
29.
30.
The in vitro activity of several new imidazoles, cloconazole, sulconazole, butoconazole, isoconazole and fenticonazole, were compared with those of amphothericin B, flucytosine, and three azoles: econazole, miconazole and ketoconazole against isolates of pathogenic Candida. A total of 186 clinical isolates of 10 species of the genus Candida and two culture collection strains were tested by an agar-dilution technique. Isoconazole was the most active azole, followed by butoconazole and sulconazole. Differences between some of the species in their susceptibility to the antifungal agents were noted. Sulconazole and cloconazole had the highest activity in vitro against 106 isolates of C. albicans. Butoconazole and isoconazole were also very active against isolates of C. albicans, and were the most active azole compounds against 80 isolates of Candida spp. 相似文献