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931.
Monosomy of chromosome No. 22. A case report 总被引:5,自引:0,他引:5
932.
933.
934.
Anticancer efficacy of the irreversible EGFr tyrosine kinase inhibitor PD 0169414 against human tumor xenografts 总被引:4,自引:0,他引:4
Vincent PW Bridges AJ Dykes DJ Fry DW Leopold WR Patmore SJ Roberts BJ Rose S Sherwood V Zhou H Elliott WL 《Cancer chemotherapy and pharmacology》2000,45(3):231-238
Purpose: The involvement of the EGF receptor (EGFr) family of receptors in cancers suggests that a selective inhibitor of the tyrosine
kinase activity of the EGFr family could have a therapeutic effect. PD 0169414, an anilinoquinazoline, is a potent irreversible
inhibitor of the EGFr family tyrosine kinase activity with IC50 values of 0.42 nM against the isolated EGF receptor, and 4.7 nM and 22 nM against EGF- and heregulin-mediated receptor phosphorylation in A431 and MDA-MB-453 cells, respectively. Methods and Results: Oral administration of 260 mg/kg per day PD 0169414 for 15 days to animals bearing advanced-stage A431 epidermoid carcinoma
produced a 28.2-day delay in tumor growth and resulted in three complete and three partial tumor regressions in six animals.
Toxicity at this dose level was limited to <6% loss of initial body weight. Doses of 160 and 100 mg/kg per day produced tumor
growth delays of 29.5 and 20.9 days and two and one complete regressions in six animals, respectively. Subcutaneous, intraperitoneal,
and oral routes of administration have also shown in vivo antitumor activity of PD 0169414 in a panel of human tumor xenografts.
Responsive tumor lines include A431 (human epidermoid carcinoma), H125 (NSCL carcinoma), MCF-7 and UISO-BCA1 (human breast
carcinoma), and SK-OV-03 (human ovarian carcinoma). The therapeutic effect ranged from delayed tumor growth (6.4 days delayed
tumor growth for 14 days of treatment) to tumor regressions (32.2 days delayed tumor growth and five partial regressions in
six animals) in these model systems. Conclusion: PD 0169414 is a specific, irreversible inhibitor of EGFr family tyrosine kinases with significant in vivo activity against
a variety of relevant human tumor xenografts.
Received: 19 May 1999 / Accepted: 11 August 1999 相似文献
935.
Purpose: A water soluble paclitaxel derivative, BMS-185660, identified previously as having parenteral activity comparable with that
of the parent drug, was evaluated for antitumor activity when given orally. Methods: Staged subcutaneous (s.c.) tumor models of both murine and human origin were used for this purpose. Results: BMS-185660 achieved levels of activity following oral administration which were comparable with those maximum effects obtained
using intravenous (i.v.) paclitaxel. Consecutive daily oral administrations of BMS-185660 resulted in maximum gross log cell
kill (LCK) values of 1.7–2.0 in two experiments involving the s.c. Madison 109 murine lung tumor model, which were comparable
with the best effects of the derivative injected intravenously, and 0.3 to 0.9 LCK greater than the maximum effects obtained
with i.v. paclitaxel; paclitaxel given orally was inactive. Against a human ovarian tumor model with developed resistance
to cisplatin (A2780/cDDP), oral BMS-185660 achieved a maximum LCK of 1.8 compared with i.v. paclitaxel, which produced a maximum
2.4 LCK. Also, in the human HCT-116 colon carcinoma model, oral BMS-185660 cured a maximum of seven of eight mice compared
with six of seven mice cured with i.v. paclitaxel. The loss in potency between comparably effective intravenously and orally
administered doses of BMS-185660 was about four- to five-fold, but since no drug-associated lethality was ever observed following
the oral administration of the highest doses of BMS-185660, further dose escalation may have been tolerated. The intermediate
metabolite between BMS-185660 and paclitaxel is BMS-181681. This compound was also evaluated orally and found not to be active
versus s.c. M109, despite demonstrating good activity by the i.v. route. Conclusion: The comparable activities of both intravenously and orally administered BMS-185660 to intravenously administered paclitaxel,
combined with the attribute of improved water solubility, provides a good basis for further derivative development.
Received: 10 September 1999 / Accepted: 16 March 2000 相似文献
936.
Dyspnea has been defined as the unpleasant sensation of difficult breathing and the reaction to that sensation. Dyspnea research, however, has largely used a unidimensional, sensory model of dyspnea devoid of the affective and motivational dimensions that uniquely characterize this sensation in clinical populations. Dyspnea might be more comprehensively viewed as a nociceptive phenomenon which, like pain, has affective dimensions expressed as distress in response to aversiveness. A multidimensional, ecologic model of the dyspnea experience is presented that incorporates nociceptive sensation properties and is suggestive of new directions for dyspnea research uniquely relevant to nursing science. 相似文献
937.
During feline postnatal development, the size of phrenic afferent neurons labelled by horseradish peroxidase was evaluated in comparison to that of the bulk of counterstained neurons located in the same cervical dorsal root ganglia (DRG) (C5-C6). From age 1 week to maturity, small and large cell components were individualized from experimental size distributions using a mathematical approach. The analysis of data in adult indicated a close correspondence between small cells and unmyelinated afferents and between large cells and myelinated afferents, respectively. From age 1 week to adulthood, mean increases in cell diameter ranged between 10 microns (small cells from phrenic afferents) and 29.5 microns (large counterstained cells). In each population, the ratio of small/large cells remained constant during growth. In contrast to data in adults, at 1 week, large phrenic neurons were bigger than the counterstained ones. At 19 weeks, the cat DRG cells had not yet reached their adult size. 相似文献
938.
939.
Rose Shija V. Bruce Sunderland Charles McDonald 《International journal of pharmaceutics》1992,80(1-3):203-211
The alkaline hydrolysis of the methyl, ethyl and n-propyl esters of 4-hydroxybenzoic acid was studied in the liquid and frozen states in sodium hydroxide solutions. The temperature range was −26 to 60°C. Significant acceleration of the reaction rate was evident in the frozen state compared with rates found at liquid state temperatures. The maximum reaction rate in the frozen state occurred in the temperature range −12 to −10°C. Methyl 4-hydroxybenzoate showed more than a 20-fold increased rate constant from 7.17 × 10−6 s−1 at 30°C to 1.53 × 10−4 s−1 at −9°C in a 1.00 × 10−2 M solution of sodium hydroxide. Rate constants in the liquid and frozen states followed pseudo first-order kinetics over 2–4 half-lives of reaction. Data were fitted to a theoretical model describing the reaction rate in the frozen state as dependent upon the increased concentration of solutes in liquid vesicles in the frozen state and the predicted reduction in the reaction rate constant with temperature decrease. Although the data exhibited similar trends to that predicted by the model, there was frequently a 50% difference in the rates observed compared with those predicted. This study has clearly demonstrated that there is a significantly increased rate of hydrolysis of these esters in the frozen state. This is a further indication that it cannot be assumed that drugs stored in solution will necessarily be stabilized, or their stability enhanced, on freezing. Storage under refrigeration conditions (4–8°C) results in enhanced shelf-lives compared with deep-freeze storage at −20°C under the conditions of this study. 相似文献
940.
Gavin McCormack Gill Lewin Brandi McCormack Edward Helmes Elizabeth Rose Fiona Naumann 《Australasian journal on ageing》2004,23(3):131-135
Background: Individuals who fear falling may restrict themselves from performing certain activities and may increase their risk of falling. Such fear, reflected in the form of falls efficacy, has been measured in only a small number of studies measuring the effectiveness of exercise interventions in the elderly. This may be due to the various types of exercise that can be performed. Hence the effectiveness of exercise on falls efficacy is relatively understudied. Therefore, there is a need to measure falls efficacy as an outcome variable when conducting exercise interventions in the elderly. Methods: A total of 43 elderly community‐dwelling volunteers were recruited and randomly allocated to a conventional exercise intervention, a holistic exercise intervention, or a control group. The interventions were performed 2 days per week for 10 weeks. Falls efficacy was measured at baseline and at the completion of the interventions using the Modified Falls Efficacy Scale (MFES). Results: Within group comparisons between baseline and follow‐up indicated no significant improvements in falls efficacy, however, the difference for the conventional exercise group approached statistical significance (baseline 8.9 to follow‐up 9.3; P = 0.058). Within group comparisons of mean difference MFES scores showed a significant difference between the conventional exercise group and the control group (conventional exercise group 0.4 vs control group ?0.6; P < 0.05). Conclusion: Given the lack of significant improvements in falls efficacy found for any of the groups, it cannot be concluded whether a conventional or a holistic exercise intervention is the best approach for improving falls efficacy. It is possible that the characteristics of the exercise interventions including specificity, intensity, frequency and duration need to be manipulated if the purpose is to bring about improvements in falls efficacy. 相似文献