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131.
132.
133.
Mary Jeanne Kreek 《Neurochemical research》1996,21(11):1469-1488
The early history of research on the possible existence of specific opioid receptors and on developing a new form of pharmacotherapy
for the treatment of heroin addiction in New York City, from 1960–1973, along with the special relationships between two leading
scientists conducting these research efforts, Dr. Eric Simon and Dr. Vincent P. Dole Jr., are presented in a historical perspective.
The linkage of these early efforts and the subsequent identification and the elucidation of the effects of exogenous opiates
acting at specific opiate receptors in human physiology, including some findings from perspective studies of heroin addicts
at time of entry to and during methadone maintenance treatment, are presented in the context of the important clues which
thereby were provided concerning the possible roles of the endogenous opioids in normal mammalian physiology. From many of
these early clinical research findings and studies in animal models, the hypothesis that the endogenous opioids system may
play an important role in stress responsivity was formulated along with the related hypothesis, first presented in the early
1970s, that an atypical responsivity to stress and stressors might be involved in the acquisition and persistence of, and
relapse to specific addictive diseases, including heroin addiction, cocaine dependency and alcoholism. More recent studies
of the possible involvement of the specific opioid receptors in these three addictive diseases—heroin addiction, cocaine addiction
and alcoholism—from our laboratory are discussed in a historical perspective of the development of these ideas from the early
research findings of not only Dr. Eric Simon, but his numerous colleagues in opioid research in the United States and throughout
the world.
Special issue dedicated to Dr. Eric J. Simon. 相似文献
134.
Cholinesterase activities in rat forebrain, erythrocytes, and plasma were assessed after a single oral administration of metrifonate
or dichlorvos. In 3-month-old rats, the dichlorvos (10 mg/kg p.o.)-induced inhibition of cholinesterase reached its peak in
brain after 15–45 min and after 10–30 min in erythrocytes and plasma. Cholinesterase activity recovered rapidly after the
peak of inhibition, but did not reach control values in brain and erythrocytes within 24 h after drug administration. The
recovery of plasma cholinesterase activity, in contrast, was already complete 12 h after dichlorvos treatment. Metrifonate
(100 mg/kg p.o.) had qualitatively similar inhibition kinetics as dichlorvos, albeit with a slightly delayed onset. Peak values
were attained 45–60 min (brain) and 20–45 min (blood), after drug administration. Apparently complete recovery of cholinesterase
activity was noted in both tissues 24 h after treatment. The dose-dependence of drug-induced inhibition of cholinesterase
in rat blood and brain was determined at the time of maximal inhibition, i.e., 30 min after dichlorvos treatment and 45 min
after metrifonate treatment. The oral ED50 values obtained for dichlorvos were 8 mg/kg for brain and 6 mg/kg for both erythrocyte and plasma cholinesterase. The corresponding
oral ED50 values for metrifonate were 10 to 15 times higher, i.e., 90 mg/kg in brain and 80 mg/kg in erythrocytes and plasma. In rats
deprived of food for 18 h before drug treatment, the corresponding ED50 values for metrifonate were 60 and 45 mg/kg, respectively, indicating an about two-fold higher sensitivity of fasted rats
to metrifonate-induced cholinesterase inhibition compared to non-fasted rats. Compared to 3-month-old rats, 19-month-old rats
showed a higher sensitivity towards metrifonate and dichlorvos. At the time of maximal inhibition, there was a strong correlation
between the degree of cholinesterase inhibition in brain and blood. These results demonstrate that single oral administration
of metrifonate and dichlorvos induces an inhibition of blood and brain cholinesterase in the conscious rat in a dose-dependent
and apparently fully reversible manner. While the efficiency of a given dose of inhibitor may vary with the satiety status
or age of the animal, the extent of brain ChE inhibition can be estimated from the level of blood ChE activity. 相似文献
135.
Twenty out of 33 Actinobacillus actinomycetemcomitans strains formed hemolytic colonies on horse blood agar plates under anaerobic conditions. The hemolytic activity found in A. actinomycetemcomitans strain 137HE was examined. This activity was detected in the late exponential to early stationary phases of growth. Human erythrocytes were the most susceptible, followed by rabbit, sheep, horse and swine red blood cells. The majority of activity was detected in the cell-associated vesicle fraction. Zwitterionic detergent 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate (CHAPS) extract from whole cells was semipurified by ammonium sulfate precipitation, preparative isoelectric focusing (IEF) and gel-filtration chromatography to yield a major band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with a molecular mass of 12 kDa. Heating at 80 C for 30 min and treatment with proteinase K or trypsin resulted in complete disappearance of the hemolytic activity. Sulphydryl reagents enhanced activity and small amounts of cholesterol inhibited it. In summary, we demonstrated the presence of hemolysin in A. actinomycetemcomitans, and examined and characterized it. 相似文献
136.
Comparison of OspA Serotypes for Borrelia burgdorferi Sensu Lato from Japan,Europe and North America
Toshiyuki Masuzawa Bettina Wilske Tetsuro Komikado Hiroyuki Suzuki Hiroki Kawabata Nanao Sato Koichi Muramatsu Nobutake Sato Emiko Isogai Hiroshi Isogai Russell C. Johnson Yasutake Yanagihara 《Microbiology and immunology》1996,40(8):539-545
Sixty-one Borrelia burgdorferi sensu lato strains from various sources (ticks, human, and wild animals) in Japan and two strains from ticks in Far Eastern Russia were classified on the basis of reactivity with 16 monoclonal antibodies (mAb) to outer surface protein A (OspA) and by DNA-DNA hybridization assay. Eleven OspA serotypes (J1 to J11) were recognized among the Japanese and the Far East Russian isolates (serotypes J1 to J9 were identified as B. garinii, serotype J10 was identified as B. afzelii, and serotype J11 corresponded to B. japonica), whereas 7 OspA serotypes for North American and European isolates previously reported (Bettina Wilske et al, J. Clin. Microbiol. 31:340-350, 1993) were not observed except for OspA serotype 2 which showed identical reactivity with OspA serotype J10. This finding provides helpful information for understanding the geographical distribution of Lyme disease borrelia and the development of vaccine and diagnostic tests. In conclusion: 1. B. burgdorferi sensu stricto has not been observed in Japan, 2. Japanese B. afzelii isolates are closely related to those from Europe, 3. B. garinii isolates from Japan are highly heterogeneous and apparently different from European B. garinii isolates. 相似文献
137.
Treatment of Gaucher disease with an enzyme inhibitor 总被引:5,自引:0,他引:5
Norman S. Radin 《Glycoconjugate journal》1996,13(2):153-157
The hypothesis is offered predicting that Caucher patients could be treated with a drug that slows the synthesis of glucosylceramide, the lipid that accumulates in this disorder. The present therapeutic approach involves augmenting the defective enzyme, glucosylceramide -glucosidase, with exogenous -glucosidase isolated from human tissue. This spectacularly expensive mode of treatment should be replaceable with a suitable enzyme inhibitor that simply slows formation of the lipid and matches the rate of synthesis with the rate of the defective, slowly working -glucosidase. Several drugs that possess this ability are available, the best known of which is 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), a designer inhibitor that resembles the synthase's substrate and product. PDMP has been found to be effective in mice, rats, fish, and a wide variety of cultured cells. Its use, at suitable dosages, seems to be harmless, although long-term tests have not been made. The lack of suitable animal models of Gaucher disease has made it difficult to test the hypothesis adequately, but PDMP does rapidly lower the levels of glucosylceramide in normal animal tissues and the animals evidently do well with the lowered levels of glucosylceramide and its more complex glycolipid metabolites.Abbreviations PDMP
1-phenyl-2-decanoylamino-3-morpholino-1-propanol
- GlcCer
glucosylceramide
- i.p.
intraperitoneal 相似文献
138.
The capacity of the oxidative pentose phosphate pathway (PPP) in the heart is limited, since the activity of glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of this pathway, is very low. Two mechanisms are involved in the regulation of this pathway. Under normal conditions, G-6-PD is inhibited by NADPH. This can be overcome in the isolated perfused rat heart by increasing the oxidized glutathione and by elevating the NADP+/NADPH ratio. Besides this rapid control mechanism, there is a long-term regulation which involves the synthesis of G-6-PD. The activity of G-6-PD was elevated in the rat heart during the development of cardiac hypertrophy due to constriction of the abdominal aorta and in the non-ischemic part of the rat heart subsequent to myocardial infarction. The catecholamines isoproterenol and norepinephrine stimulated the activity of myocardial G-6-PD in a time- and dose-dependent manner. The isoproterenol-induced stimulation was cAMP-dependent and due to increased new synthesis of enzyme protein. The G-6-PD mRNA was elevated by norepinephrine. As a consequence of the stimulation of the oxidative PPP, the available pool of 5-phosphoribosyl-l-pyrophosphate (PRPP) was expanded. PRPP is an important precursor substrate for purine and pyrimidine nucleotide synthesis. The limiting step in the oxidative PPP, the G-6-PD reaction, can be bypassed with ribose. This leads to an elevation of the cardiac PRPP pool. The decline in ATP that is induced in many pathophysiological conditions was attenuated or even entirely prevented by i.v. infusion of ribose. In two in vivo rat models, the overloaded and catecholamine-stimulated heart and the infarcted heart, the normalization of the cardiac adenine nucleotide pool by ribose was accompanied by an improvement of global heart function. Combination of ribose with adenine or inosine in isoproterenol-treated rats was more effective to restore completely the cardiac ATP level within a short period of time than either intervention alone. (Mol Cell Biochem 160/161: 101–109, 1996) 相似文献
139.
140.
A crown rot disease in wheat caused by the fungusFusarium graminearum Schw. Group 1 is a widespread problem in chronically Zn-deficient Australian soils. A link between crown rot and Zn deficiency
was established by Sparrow and Graham (1988). This paper reports a test of a further hypothesis, that wheat genotypes more
efficient at extracting zinc from low-zinc soils are more resistant to infection by this pathogen. Three wheat cultivars (Excalibur,
Songlen and Durati) of differential Zn efficiency were tested at three zinc levels (0.05, 0.5 and 2.0 mg Zn kg−1 of soil) and three levels ofF. graminearum S. Group 1 inoculum (0.1 g and 0.3 g kg−1 live chaff-inoculum and control having 0.1 g kg−1 dead chaff inoculum). Six weeks after sowing dry matter production of shoots and roots was decreased byFusarium inoculation at 0.05 mg and 0.5 mg kg−1 applied Zn.Fusarium inoculum at 0.1 g was as effective as 0.3 g kg−1 for infection and decreasing dry matter. The infection at the basal part of culm decreased significantly by increasing the
rate of Zn application. Excalibur, a Zn-efficient cultivar (tolerant to Zn deficiency) produced significantly more shoot and
root dry matter, and showed less disease infection compared with Zn-inefficient cultivars (Durati and Songlen) at low (0.05
mg Zn kg−1 soil) and medium (0.5 mg Zn kg−1 soil) Zn fertilization rates. Higher rate of Zn fertilization (2.0 mg Zn kg−1 soil) reduced the disease level in Durati to the level of Excalibur but the disease level of Songlen was still high, indicating
its high Zn requirement and or sensitivity to crown rot. The data on Zn uptake show that Excalibur, being Zn-efficient, was
able to scavenge enough Zn from Zn-deficient soil, we suggest that besides sustaining growth Excalibur was able to build and
maintain resistance to the pathogen; inefficient cultivars needed extra Zn fertilization to achieve performance comparable
to that of Excalibur. The present study indicates that growing Zn-efficient cultivars of wheat along with judicious use of
Zn fertilizer in Zn-deficient areas where crown rot is a problem may sustain wheat production by reducing the severity of
the disease as well as by increasing the plant vigour through improved Zn nutrition. ei]Section editor: R Rodriques-Kalana 相似文献