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81.
Takuma Narita Shingo Hatakeyama Shintaro Narita Masahiro Takahashi Toshihiko Sakurai Sadafumi Kawamura Senji Hoshi Jiro Shimoda Toshiaki Kawaguchi Shigeto Ishidoya Koji Mitsuzuka Yoichi Arai Akihiro Ito Norihiko Tsuchiya Tomonori Habuchi Chikara Ohyama 《Translational andrology and urology》2021,10(1):417
BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC. 相似文献
82.
Key words dysrhythmia - isorhythmic dissociation - oscillation 相似文献
83.
We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman
who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant.
The tumor was elastic and soft, smooth surfaced, well-defined and mobile. Dimpling sign or change of skin color were not observed.
Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended
surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin
and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in
the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of
angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the
cervical and thoracic vertebrae were observed and radiation therapy was performed. Sixteen months from onset, she died due
to multi-organ failure as general metastases of angiosarcoma. At autopsy, metastases to many organs including the digestive
system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized
the difficulties in clinical diagnosis and treatment for the angiosarcoma of the breast. 相似文献
84.
Toshiaki Minami Emiko Okuda-Ashitaka Mikio Nishizawa Hidemaro Mori Seiji Ito 《British journal of pharmacology》1997,122(4):605-610
- We recently showed that intrathecal administration of nociceptin induced allodynia by innocuous tactile stimuli and hyperalgesia by noxious thermal stimuli in conscious mice. In the present study, we examined the effect of prostaglandins on nociceptin-induced allodynia and hyperalgesia.
- Prostaglandin D2 (PGD2) blocked the allodynia induced by nociceptin in a dose-dependent manner with an IC50 of 26 ng kg−1, but did not affect the nociceptin-induced hyperalgesia at doses up to 500 ng kg−1. BW 245C (an agonist for PGD (DP) receptor) blocked the allodynia with an IC50 of 83 ng kg−1.
- The blockade of nociceptin-induced allodynia by PGD2 was reversed by the potent and selective DP-receptor antagonist BW A868C in a dose-dependent manner with an ED50 of 42.8 ng kg−1.
- Glycine (500 ng kg−1) almost completely blocked the nociceptin-induced allodynia. A synergistic effect on the inhibition of nociceptin-evoked allodynia was observed between glycine and PGD2 at below effective doses.
- Dibutyryl cyclic AMP, but not dibutyryl cyclic GMP, blocked the nociceptin-induced allodynia with an IC50 of 2.9 μg kg−1.
- PGE2, PGF2α, butaprost (an EP2 agonist) and cicaprost (a PGI receptor agonist) did not affect the nociceptin-induced allodynia.
- These results demonstrate that PGD2 inhibits the nociceptin-evoked allodynia through DP receptors in the spinal cord and that glycine may be involved in this inhibition.
85.
Toshiaki Sato Toshio Obata Yasumitsu Yamanaka Makoto Arita 《British journal of pharmacology》1997,122(4):611-618
- Adenosine exerts cardioprotective effects on the ischaemic myocardium. The production of adenosine in the ischaemic myocardium is attributed primarily to the enzymatic dephosphorylation of adenosine 5′-monophosphate (AMP) by 5′-nucleotidase. We determined the activity of 5′-nucleotidase in rat hearts. The objective of the study was to determine the effects of ATP-sensitive K+ (KATP) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique.
- Rats were anaesthetized and the microdialysis probe was implanted in the left ventricular myocardium, followed by perfusion with Tyrode solution. The baseline level of dialysate adenosine was 0.51±0.09 μM (n=16). Introduction of AMP (100 μM) through the probe increased the dialysate adenosine markedly to 9.79±0.43 μM (n=12, P<0.001 vs baseline), and this increase was inhibited by the ecto-5′-nucleotidase inhibitor, α,β-methyleneadenosine 5′-diphosphate (100 μM), to 0.76±0.12 μM (n=8). Thus, the dialysate adenosine noted during the perfusion of AMP originated from dephosphorylation of AMP by ecto-5′-nucleotidase, and the dialysate level of adenosine attained reflects the ecto-5′-nucleotidase activity in the tissue in situ.
- Glibenclamide (0.1–100 μM) decreased the adenosine concentration measured during the perfusion of AMP (100 μM) in a concentration-dependent manner (IC50=10.5 μM). In contrast, 5-hydroxydecanoate (10–100 μM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 μM). These results suggest that glibenclamide inhibits the activity of endogenous ecto-5′-nucleotidase and decreases the concentration of adenosine in the interstitial space of rat ventricular muscles in situ.
86.
To investigate whether adenohypophysial hormone expression is heterogeneous within individual clinically nonfunctioning pituitary
adenomas, immunohistochemical examinations were performed on tissues obtained by multiple sampling of 11 adenomas. Stained
sections were assessed by morphometric image analysis as well as semiquantitative estimation under microscopy. All tumors
except one were immunopositive for one or more gonadotropins. Results were divided into five grades based on the proportion
of immunoreactive cells per section. Semiquantitative estimation showed only a one-grade difference among samples from the
same tumor in four cases for FSHβ and in two cases for LHβ. These qualitative similarities between multiple samples were confirmed
by morphometric image analysis.
From the practical standpoint of making a diagnosis of nonfunctioning pituitary adenoma, it is not necessary to take into
account immunohistochemical heterogeneity within an individual tumor, and immunohistochemical findings in a given sample obtained
at surgery can be regarded as representative of the entire adenoma. 相似文献
87.
Saeki Toshiaki; Salomon David S.; Johnson Gibbes R.; Gullick Willium J.; Mandai Koichi; Yamagam Keitaro; Moriwaki Shosuke; Tanada Minoru; Takashima Shigemitsu; Tahara Eiichi 《Japanese journal of clinical oncology》1995,25(6):240-249
The frequency of expression and localization of cripto-1 (CR-1),amphiregulin (AR), transforming growth factor alpha (TGF), epidermalgrowth factor receptor (EGFR) and erbB-2 were examined by immunohistochemistryin 45 carcinomas and adjacent non-involved normal colon mucosa.Thirty (66.7%), 24 (53.3%), 23 (51.1%), 23 (51.1%) and 13 (28.9%)of the 45 carcinomas showed positive staining for CR-1, AR,TGF, EGFR and erbB-2, respectively, whereas 7 (15.5%), 17 (37.7%),15 (33.3%), 20 (44.4%) and 0 (0%) of the corresponding non-involvednormal mucosa specimens were reactive. Among 13 carcinomas withlymph node involvement, 10 (76.9%), 8 (61.5%), 10 (76.9%), 8(61.5%) and 7 (53.8%) exhibited positive staining for CR-1,AR, TGF-, EGFR and erbB-2, respectively. There was a statisticallysignificant association between the frequency of either TGF(P<0.05) or erbB-2 (P<0.05) expression and lymph nodemetastasis. In addition, a signficantly higher frequency ofpositive staining for TGF was observedin Dukes' grade C carcinomas(P<0.05). Finally, significant trends for coexpression ofEGFR and either TGF (P<0.01) or AR (P<0.05) were detectedin carcinomas. These data suggest that AR and TGF may play animportant role in the development of colorectal carcinomas throughan autocrine mechanism involving EGFR, and demonstrate thatTGF and erbB-2 may be more reliable indicators of metastasisor prognosis than CR-1, AR or EGFR in human colon cancers. 相似文献
88.
Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) stimulate osteoclastic bone resorption 总被引:3,自引:0,他引:3
Shibutani T Yamashita K Aoki T Iwayama Y Nishikawa T Hayakawa T 《Journal of bone and mineral metabolism》1999,17(4):245-251
As both tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 have been reported to inhibit bone resorption, we examined
whether TIMP-1 or TIMP-2 in fetal calf serum (FCS), with which culture media were supplemented, affected osteoclastic bone
resorption in vitro. Contrary to our expectation, almost complete suppression of osteoclastic bone resorption was observed
when both TIMP-1 and TIMP-2 were removed from the FCS. Bone resorption was, however, almost fully restored by the addition
of recombinant TIMPs. TIMPs stimulate bone resorption at significantly lower concentrations (∼ng/ml) than those (∼μg/ml) required
to inhibit bone resorption. To understand the mechanism of TIMP-dependent bone resorption, we counted and compared the number
of tartrate-resistant acid phosphatase-(TRAP-) positive and multinuclear cells in cultures containing either 10% FCS or TIMP-1-free
and/or TIMP-2-free FCS. There was essentially no difference in number among these, suggesting that the TIMP role seems to
be related to the functional expression of osteoclasts. Metallo-proteinase inhibitors, either BE16627B[l-N-(N-hydroxy-2-isobutylsuccinynamoyl)-seryl-l-valine] or R94138 {N-methyl-(3S)-2-[(2R)-2-hydroxycarbamoylmethylundecanoyl] hexahydropyridazine-3-carboxamide}, could not replace TIMPs, suggesting that the osteoclast-stimulating
activity of TIMPs cannot be ascribed to merely their inhibitory effect on matrix metalloproteinases.
Received: Oct. 15, 1998 / Accepted: April 5, 1999 相似文献
89.
The ultrastructure of parapapillary chorioretinal atrophy in eyes with secondary angle closure glaucoma 总被引:4,自引:0,他引:4
Toshiaki Kubota Ursula M. Schlötzer-Schrehardt Gottfried O. H. Naumann Toshihiko Kohno Hajime Inomata 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1996,234(6):351-358
Background: The present study was performed to investigate the ultrastructure of deep retinal layers and choroid corresponding to the parapapillary chorioretinal atrophy in eyes with secondary angle-closure glaucoma. Methods: The glaucomatous eyes included two eyes enucleated due to iris ring melanoma with high intraocular pressure and one eye with neovascular glaucoma enucleated due to ocular pain. The control eyes included one eye enucleated due to choroidal malignant melanoma with normal intraocular pressure and one eye enucleated during surgery for supramandibular carcinoma. These eyes were studied with light and electron microscopy. Results: In the region of parapapillary chorioretinal atrophy of glaucomatous eyes, the retinal pigment epithelial cells showed degenerative changes, such as loss of basal in foldings and microvilli, degenerated mitochondria, vacuolar degeneration and irregular distribution of melanin granules. The photoreceptors were decreased in number in this area of glaucomatous eyes. The lumen of the choriocapillary vessels adjacent to the optic nerve was collapsed. Conclusion: These results elucidate the fine structures of deep retina and choroid in the region of parapapillary chorioretinal atrophy of glaucomatous eyes, and suggest that the reduced choroidal perfusion might be the pathogenetic mechanism of glaucomatous parapapillary chorioretinal atrophy. 相似文献
90.
Akio Kanetoshi Eiji Katsura Hiroshi Ogawa Tohru Ohyama Hiroyasu Kaneshima Toshiaki Miura 《Archives of environmental contamination and toxicology》1992,23(1):91-98
Acute toxicity of 2,4,4-trichloro-2-hydroxydiphenyl ether (Irgasan® DP300) (I) and its three chlorinated derivatives, 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD50 values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively.The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11–76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives.The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene. 相似文献