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71.
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Arif JM; Gairola CG; Glauert HP; Kelloff GJ; Lubet RA; Gupta RC 《Carcinogenesis》1998,19(8):1515-1517
The present study investigated the effects of dietary oltipraz on cigarette
smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats
were exposed daily to sidestream cigarette smoke in a whole- body exposure
chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained
on control diet while another group received the same diet supplemented
with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz,
starting 1 week prior to initiation of smoke exposure until the end of the
experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated
32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5
predominated in both the lung and the heart while adduct nos 3 and 2
predominated in the trachea and bladder, respectively. Quantitative
analysis revealed that the total adduct level was the highest in lungs
(270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48
adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides)
and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz
treatment reduced the adduct levels in lungs and bladder by >60%, while
the reduction in lungs in the low-dose group was approximately 35%. In
trachea, the effect of low and high dietary oltipraz on smoke DNA adduction
was equivocal, while smoke-related DNA adducts in the heart were minimally
inhibited by high-dose oltipraz. In a repeat experiment that employed a
3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to
inhibit the formation of DNA adducts in rat lungs and trachea by 80 and
65%, respectively. These data clearly demonstrate a high efficacy of
oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts
in the target tissues.
相似文献
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Kalinichev M Rosenblatt JS Nakabeppu Y Morrell JI 《The Journal of comparative neurology》2000,416(1):45-78
Juvenile rats can exhibit maternal behavior after being exposed continuously to rat pups, a process called sensitization. Maternal behavior in juveniles is robust and is similar to adult maternal behavior (Mayer and Rosenblatt [1979] Dev. Psychobiol. 12:407-424; Gray and Chesley [684] J. Comp. Psychol. 98:91-99). In this study, immunocytochemical detection of the protein products of two immediate-early genes, c-fos and fosB, was used as a tool to identify forebrain neuronal populations involved in the maternal behavior of 27-day-old juvenile rats compared with 60-day-old adults. To sensitize them, rats were exposed continuously to foster pups. Once they were maternal, they were isolated from pups overnight, reexposed to pups for 2 hours, and then killed. Nonmaternal control animals also were isolated overnight and were either reexposed to pups for 2 hours or kept isolated from pups before killing. The lateral habenula (LH) was the only area in which both maternal juveniles and maternal adults had more c-Fos-immunoreactive (-Ir) neurons compared with controls. In maternal adults, the number of neurons that expressed c-Fos and FosB immunoreactivity increased in the medial preoptic area (MPO) and the ventral bed nucleus of the stria terminalis (BSTv), whereas the dorsal bed nucleus of the stria terminalis (BSTd) and the medial and cortical nuclei of the amygdala (MEA and COA, respectively) had increases only in the number of neurons that expressed c-Fos immunoreactivity. In contrast, juveniles, whether or not they were maternal, had the same number of c-Fos-IR and FosB-Ir neurons in all these areas. The adult-like increase in the number of c-Fos-Ir neurons found in maternal juveniles suggests that the juvenile LH participates in the neural circuit that supports maternal behavior in an adult-like manner. The lack of c-fos or fosB induction in the MPO, BSTv, BSTd, COA, or MEA of maternal juveniles compared with maternal adults may reflect the immaturity of these brain regions in juvenile rats. Exactly what this immaturity consists of and when the responses of these regions become adult-like remain to be determined. 相似文献
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RA D. Wüstenberg 《Der Gyn?kologe》2006,39(10):824-828
Some of the girls who live in Germany and have Muslim parents are threatened by female genital mutilation. This report describes the kinds and medical consequences of female genital mutilation as well as the criminal judgement. Female genital mutilation is considered as dangerous bodily harm, not as grievous bodily harm. Consent does not justify the infringement of rights. The argument that Islam justifies the infringement of rights is irrelevant by law. The human right of bodily intactness has priority over the right of religious freedom. Finally the legal regulations about dealing with personal data are presented. A legal compulsory registration still does not exist. 相似文献
78.
A. Barazza A. Wittelsberger N. Fiori E. Schievano S. Mammi C. Toniolo J.M. Alexander M. Rosenblatt E. Peggion M. Chorev 《Chemical biology & drug design》2005,65(1):23-35
Abstract: The N‐terminal 1–34 segment of parathyroid hormone (PTH) is fully active in vitro and in vivo and it can reproduce all biological responses in bone characteristic of the native intact PTH. Recent studies have demonstrated that N‐terminal fragments presenting the principal activating domain such as PTH(1–11) and PTH(1–14) with helicity‐enhancing substitutions yield potent analogues with PTH(1–34)‐like activity. To further investigate the role of α‐helicity on biological potency, we designed and synthesized by solid‐phase methodology the following hPTH(1–11) analogues substituted at positions 1 and/or 3 by the sterically hindered and helix‐promoting Cα‐tetrasubstituted α‐amino acids α‐amino isobutyric acid (Aib), 1‐aminocyclopentane‐1‐carboxylic acid (Ac5c) and 1‐aminocyclohexane‐1‐carboxylic acid (Ac6c): Ac5c‐V‐Aib‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( I ); Aib‐V‐Ac5c‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( II ); Ac6c‐V‐Aib‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( III ); Aib‐V‐Ac6c‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( IV ); Aib‐V‐Aib‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( V ); S‐V‐Aib‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( VI ), S‐V‐Ac5c‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( VII ); Ac5c‐V‐S‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( VIII ); Ac6c‐V‐S‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( IX ); Ac5c‐V‐Ac5c‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( X ); Ac6c‐V‐Ac6c‐E‐I‐Q‐L‐M‐H‐Q‐R‐NH2 ( XI ). All analogues were biologically evaluated and conformationally characterized in 2,2,2‐trifluoroethanol (TFE) solution by circular dichroism (CD). Analogues I – V , which cover the full range of biological activity observed in the present study, were further conformationally characterized in detail by nuclear magnetic resonance (NMR) and computer simulations studies. The results of ligand‐stimulated cAMP accumulation experiments indicated that analogues I and II are active, analogues III , VI and VII are very weakly active and analogues IV , V , VIII–XI are inactive. The most potent analogue, I exhibits biological activity 3500‐fold higher than that of the native PTH(1–11) and only 15‐fold weaker than that of the native sequence hPTH(1–34). Remarkably, the two most potent analogues, I and II , and the very weakly active analogues, VI and VII , exhibit similar helix contents. These results indicate that the presence of a stable N‐terminal helical sequence is an important but not sufficient condition for biological activity. 相似文献
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