全文获取类型
收费全文 | 20541篇 |
免费 | 1304篇 |
国内免费 | 38篇 |
专业分类
耳鼻咽喉 | 128篇 |
儿科学 | 690篇 |
妇产科学 | 709篇 |
基础医学 | 2750篇 |
口腔科学 | 269篇 |
临床医学 | 3395篇 |
内科学 | 3879篇 |
皮肤病学 | 212篇 |
神经病学 | 2043篇 |
特种医学 | 308篇 |
外科学 | 1574篇 |
综合类 | 272篇 |
一般理论 | 31篇 |
预防医学 | 2827篇 |
眼科学 | 151篇 |
药学 | 1208篇 |
中国医学 | 13篇 |
肿瘤学 | 1424篇 |
出版年
2023年 | 90篇 |
2022年 | 163篇 |
2021年 | 337篇 |
2020年 | 214篇 |
2019年 | 378篇 |
2018年 | 397篇 |
2017年 | 282篇 |
2016年 | 358篇 |
2015年 | 412篇 |
2014年 | 607篇 |
2013年 | 971篇 |
2012年 | 1399篇 |
2011年 | 1404篇 |
2010年 | 773篇 |
2009年 | 763篇 |
2008年 | 1379篇 |
2007年 | 1350篇 |
2006年 | 1359篇 |
2005年 | 1389篇 |
2004年 | 1321篇 |
2003年 | 1298篇 |
2002年 | 1260篇 |
2001年 | 182篇 |
2000年 | 166篇 |
1999年 | 205篇 |
1998年 | 255篇 |
1997年 | 222篇 |
1996年 | 182篇 |
1995年 | 194篇 |
1994年 | 171篇 |
1993年 | 170篇 |
1992年 | 161篇 |
1991年 | 143篇 |
1990年 | 133篇 |
1989年 | 127篇 |
1988年 | 127篇 |
1987年 | 131篇 |
1986年 | 106篇 |
1985年 | 105篇 |
1984年 | 143篇 |
1983年 | 101篇 |
1982年 | 129篇 |
1981年 | 113篇 |
1980年 | 111篇 |
1979年 | 77篇 |
1978年 | 73篇 |
1977年 | 53篇 |
1976年 | 53篇 |
1975年 | 47篇 |
1974年 | 50篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
901.
902.
903.
Lash LH Putt DA Hueni SE Cao W Xu F Kulidjian SJ Horwitz JP 《Biochemical pharmacology》2002,64(10):1533-1546
Cellular energetics and redox status were evaluated in NRK-52E cells, a stable cell line derived from rat proximal tubules. To assess toxicological implications of these properties, susceptibility to apoptosis induced by S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a well-known mitochondrial and renal cytotoxicant, was studied. Cells exhibited high activities of several glutathione (GSH)-dependent enzymes, including gamma-glutamylcysteine synthetase, GSH peroxidase, glutathione disulfide reductase, and GSH S-transferase, but very low activities of gamma-glutamyltransferase and alkaline phosphatase, consistent with a low content of brush-border microvilli. Uptake and total cellular accumulation of [14C]alpha-methylglucose was significantly higher when cells were exposed at the basolateral as compared to the brush-border membrane. Similarly, uptake of GSH was nearly 2-fold higher across the basolateral than the brush-border membrane. High activities of (Na(+)+K(+))-ATPase and malic dehydrogenase, but low activities of other mitochondrial enzymes, respiration, and transport of GSH and dicarboxylates into mitochondria were observed. Examination of mitochondrial density by confocal microscopy, using a fluorescent marker (MitoTracker Orange), indicated that NRK-52E cells contain a much lower content of mitochondria than rat renal proximal tubules in vivo. Incubation of cells with DCVC caused time- and concentration-dependent ATP depletion that was largely dependent on transport and bioactivation, as observed in the rat, on induction of apoptosis, and on morphological damage. Comparison with primary cultures of rat and human proximal tubular cells suggests that the NRK-52E cells are modestly less sensitive to DCVC. In most respects, however, NRK-52E cells exhibited functions similar to those of the rat renal proximal tubule in vivo. 相似文献
904.
Schimana J Gebhardt K Höltzel A Schmid DG Süssmuth R Müller J Pukall R Fiedler HP 《The Journal of antibiotics》2002,55(6):565-570
New lipopeptide antibiotics, colourless arylomycins A series and yellow arylomycins B series were detected in the culture filtrate and mycelium extracts of Streptomyces sp. Tü 6075 by HPLC-diode-array and HPLC-electrospray-mass-spectrometry screening. Arylomycins are a family of lipohexapeptide antibiotics, which represent the first examples of biaryl-bridged lipopeptides. They show antibiotic activities against Gram-positive bacteria. 相似文献
905.
Houlihan WJ Kelly L Pankuch J Koletar J Brand L Janowsky A Kopajtic TA 《Journal of medicinal chemistry》2002,45(19):4097-4109
A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers. 相似文献
906.
Bryant SD George C Flippen-Anderson JL Deschamps JR Salvadori S Balboni G Guerrini R Lazarus LH 《Journal of medicinal chemistry》2002,45(25):5506-5513
The crystal structures of three analogues of the potent delta-opioid receptor antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosine-L-1,2,3,4-tetrahydroisoquinoline-3-carboxylate), N,N (CH(3))(2)-Dmt-Tic-OH (1), H-Dmt-Tic-NH-1-adamantane (2), and N,N(CH(3))(2)-Dmt-Tic-NH-1-adamantane (3) were determined by X-ray single-crystal analysis. Crystals of 1 were grown by slow evaporation, while those of 2 and 3 were grown by vapor diffusion. Compounds 1 and 3 crystallized in the monoclinic space group P2(1), and 2 crystallized in the tetragonal space group P4(3). Common backbone atom superimpositions of structures derived from X-ray diffraction studies resulted in root-mean-square (rms) deviations of 0.2-0.5 A, while all-atom superimpositions gave higher rms deviations from 0.8 to 1.2 A. Intramolecular distances between the aromatic ring centers of Dmt and Tic were 5.1 A in 1, 6.3 A in 2, and 6.5 A in 3. The orientation of the C-terminal substituent 1-adamantane in 2 and 3 was affected by differences in the psi torsion angles and strong hydrogen bonds with adjacent molecules. Despite the high delta-opioid receptor affinity exhibited by each analogue (K(i) < 0.3 nM), high mu receptor affinity (K(i) < 1 nM) was manifested only with the bulky C-terminal 1-adamantane analogues 2 and 3. Furthermore, the bioactivity of both 2 and 3 exhibited mu-agonism, while 3 also had potent delta-antagonist activity. Those data demonstrated that a C-terminal hydrophobic group was an important determinant for eliciting mu-agonism, whereas N-methylation maintained delta-antagonism. Furthermore, the structural results support the hypothesis that expanded dimensions between aromatic nuclei is important for acquiring mu-agonism. 相似文献
907.
p75-nerve growth factor as an antiapoptotic complex: independence versus cooperativity in protection from enediyne chemotherapeutic agents 总被引:4,自引:0,他引:4
Yan C Liang Y Nylander KD Wong J Rudavsky RM Saragovi HU Schor NF 《Molecular pharmacology》2002,61(4):710-719
Growth factors, including nerve growth factor (NGF), have been hypothesized to play a role in resistance to chemotherapeutic agent-induced apoptosis. Induction by NGF of resistance to apoptosis is primarily thought to be the result of its binding to its high-affinity receptor, TrkA. The low-affinity NGF receptor, p75, has long been thought merely to facilitate NGF binding to TrkA. However, we have previously shown that the binding of NGF to its low-affinity receptor, p75, protects neuroblastoma cells that do not express TrkA against apoptosis induced by enediyne chemotherapeutic agents. In cells that express both receptors, it is not clear what determines which receptor is responsible for the protective effect of NGF. We now show that, in enediyne-treated SH-SY5Y neuroblastoma transfectants with native levels of p75 and a low TrkA/p75 ratio (1/100), the anti-apoptotic effect of NGF requires binding to p75. In contrast, in transfectants with native levels of p75 and a high TrkA/p75 ratio (100/100), NGF treatment prevents enediyne-induced apoptosis by a mechanism independent of p75 binding. Treatment of low TrkA/p75 ratio cells with NGF results in activation and nuclear translocation of NF-kappaB and tyrosine phosphorylation of TrkA. Analogous treatment of high TrkA/p75 ratio cells results only in phosphorylation of TrkA even though nuclear factor (NF)-kappaB signaling is not inactive and can be initiated by other ligands. The ratio of TrkA/p75 in cells that express both receptors probably contributes to the determination of which of the two known roles of p75 (i.e., TrkA independent or TrkA facilitatory) are responsible for NGF-mediated protection from enediyne-induced apoptosis. 相似文献
908.
Volcanic ashes from Arizona and Hawaii, with chemical and mineral properties similar to those of lunar and Martian soils, respectively, are used by the National Aeronautics and Space Administration (NASA) to simulate lunar and Martian environments for instrument tests. NASA needs toxicity data on these volcanic soils to assess health risks from potential exposures of workers in facilities where these soil simulants are used. In this study we investigated the acute effects of lunar soil simulant (LSS) and Martian soil simulant (MSS), as a complement to a histopathological study assessing their subchronic effects (Lam et al., 2002). Fine dust of LSS, MSS, TiO(2), or quartz suspended in saline was intratracheally instilled into C57Bl/6J mice (4/group) in single doses of 0.1 mg/mouse or 1 mg/mouse. The mice were euthanized 4 or 24 h after the dust treatment, and bronchoalveolar lavage fluid (BALF) was obtained. Statistically significant lower cell viability and higher total protein concentration in the BALF were seen only in mice treated with the high dose of quartz for 4 h and with the high dose of MSS or quartz for 24 h, compared to mice treated only with saline. A significant increase in the percentage of neutrophils was not observed with any dust-treated group at 4 h after the instillation, but was observed after 24 h in all the dust-treated groups. This observation indicates that these dusts were not acutely toxic and the effects were gradual; it took some time for neutrophils to be recruited into and accumulate significantly in the lung. A statistically significant increase in apoptosis of lavaged macrophages from mice 4 h after treatment was found only in the high-dose silica group. The overall results of this study on the acute effects of these dusts in the lung indicate that LSS is slightly more toxic than TiO(2), and that MSS is comparable to quartz. These results were consistent with the subchronic histopathological findings in that the order of severity of lung toxicity was TiO(2) < LSS < MSS < quartz. 相似文献
909.
Exploring the domains of appropriateness of drug therapy, using the Nominal Group Technique 总被引:2,自引:0,他引:2
Objective: To explore the domains encompassed within the assessment of the appropriateness of prescribing for an individual patient.Method: The Nominal Group Technique was used to address the question "How can we assess inappropriate drug therapy of individual patients that is responsive to pharmaceutical care?" The group participants were a self-selected group of nine pharmacists and one pharmacologist attending an international working conference on the Outcomes of Pharmaceutical Care. Item generation was followed by discussion for clarification and operationalisation. Voting achieved a consensus, defined as 70%, agreement on the importance of items for inclusion in an instrument to assess appropriateness.Results: Sixty-seven items were initially generated. During discussion, similar items were combined and items were grouped into domains. Items that considered the patient's perspective were commonly suggested, but many were discarded after discussing their operationalisation. Consensus was obtained that eighteen items, in seven domains, should be included in the instrument. The domains were indication and drug choice (5 items), effectiveness (2), risks and safety (2), dosage (3), interactions (1), practical use (4), and monitoring (1).Conclusion: It is hoped that, with adequate testing, these indicators of appropriateness of prescribing can be used by pharmacists to begin to routinely assess the impact of pharmaceutical care on the quality of prescribing for patients under their care. 相似文献
910.
Rats discriminated the novel antipsychotic quetiapine (Seroquel). Full generalization was seen with the novel ("atypical") antipsychotics, clozapine, olanzapine, and risperidone. Generalization was not seen with the older "typical" antipsychotics, haloperidol, chlorpromazine, and loxapine, or with the novel atypical antipsychotic, amisulpride. The pattern of generalization resembled that seen in rats trained to discriminate a low dose (1.25 mg/kg) of clozapine, which dissociates most novel antipsychotics from typical antipsychotics. However, the failure of the novel antipsychotic amisulpride to generalize demonstrates that this bioassay does not detect all novel antipsychotics. These data suggest that the discrimination of antipsychotics such as quetiapine may be of value in the development of novel antipsychotics, although the relationship between the discriminative properties of such drugs and their clinical actions is unclear. 相似文献